Carnosine > Re : AGING: Accumulation of DNA damage

From: \[ Robert-Coyote \] (
Date: Tue Jul 18 2000 - 10:25:15 MDT

copyed from LEF forum

Michael Rae 16-Jul-00, 06:48 PM (EDT)
1. "RE: Carnosine"
Hi, Tom:
>50 mg of carnosine is useless. You need over 10 times that much to be of
>any value. 6 ChronoForte caps contain 1000 mg.

Similarly, the product description for this product says that a metabolizing
enzyme (carnosinase) will make amounts less than 1 g/day useless. What is
the basis for these dosing reccomendations?


[A very good question which I have been wanting to get around to finding
This question illustrates the reason why I wanted to have every statement of
claim in the new Product Directory footnoted with a citation reference
number. However, LEF refuses to do that with any of their articles or even
their protocols, prefering instead to simply lump together all supporting
references at the end. For the products, it is much worse, they do not even
put references for claims in the Directory at all!
Searching medline has not produced a complete answer (which made be in the
full text of some of the papers) but the following abstracts are relevant.
Since "Human tissue carnosinase is a non-specific dipeptidase, actively
hydrolysing many dipeptides, including prolinase substrates." it seems to me
that supplementing other safe and cheap dipeptidases (if such are available)
would spare the hydrolysis of carnosine and make lower doses effective.
While searching medline and reading about the effects of carnosinase (there
are diseases of carnosinase deficiency), however, I also became concerned
about the effects of having it, in effect, continuously inhibited by keeping
it saturated by carnosine mega-supplementation (for example see the last
abstract below).

Biochemistry (Mosc) 2000 May;65(5):588-598
The Natural Histidine-Containing Dipeptide Nalpha-Acetylcarnosine as an
Antioxidant for Ophthalmic Use.
Babizhayev MA, Yermakova VN, Semiletov YA, Deyev AI
Innovative Vision Products Inc., County of New Castle, Delaware, 19810, USA.

The naturally occurring compound Nalpha-acetylcarnosine is proposed as a
prodrug of L-carnosine that is resistant to enzymatic hydrolysis by
carnosinase. Eyes of rabbits were treated with 1% Nalpha-acetylcarnosine,
L-carnosine, or placebo and extracts of the aqueous humor from the anterior
eye chamber were analyzed for imidazole content by reverse-phase analytical
high performance liquid chromatography (HPLC) and thin-layer (TLC) and
ion-exchange chromatographic techniques. Topical administration of pure
L-carnosine to the rabbit eye did not lead to accumulation of this compound
in the aqueous humor over 30 min in concentration exceeding that in the
placebo-treated matched eye. Nalpha-Acetylcarnosine showed dose-dependent
hydrolysis in its passage from the cornea to the aqueous humor, releasing
L-carnosine after l5-30 min of ocular administration of the prodrug in a
series of therapeutic modalities: instillation PMID: 10851037

Clin Chim Acta 1994 Feb;225(1):57-64
Serum carnosinase activities in central nervous system disorders.
Wassif WS, Sherwood RA, Amir A, Idowu B, Summers B, Leigh N, Peters TJ
Dept. of Clinical Biochemistry, King's College School of Medicine and
Dentistry, London, UK.

Serum carnosinase activity was assayed in five groups of patients with
neurological disorders. Enzyme activities in patients with idiopathic
epilepsy (mean +/- S.E.M., 148 +/- 11 nmol/ml per min) and motor neurone
disease (155 +/- 15 nmol/ml per min) were similar to the control group (161
+/- 7 nmol/ml per min). Reduced serum carnosinase activity was observed in
patients with Parkinson's disease (109 +/- 11 nmol/ml per min, P < 0.005),
multiple sclerosis (82.5 +/- 10.0 nmol/ml per min, P < 0.005) and patients
following a cerebrovascular accident (74.6 +/- 5.4 nmol/ml per min, P <
0.001) compared with the control group. Carnosinase activity, 5-10% of that
found in serum, was detected in CSF samples. The cause of reduced serum
carnosinase activities in central nervous system disorders is unclear,
although anoxic damage to carnosinase-producing cells or disruption of the
blood-brain barrier may be responsible.
PMID: 8033354, UI: 94306681

J Physiol (Lond) 1991 Aug;439:411-22
Intestinal absorption of the intact peptide carnosine in man, and comparison
with intestinal permeability to lactulose.
Gardner ML, Illingworth KM, Kelleher J, Wood D
Department of Biomedical Sciences, University of Bradford.

1. Healthy humans ingested the dipeptide carnosine
(L-beta-alanyl-L-histidine). Their plasma levels and urinary outputs of
carnosine and beta-alanine were monitored over the following 5 h. 2. Large
amounts of intact carnosine (up to 14% of the ingested dose) were recovered
in the urine over the 5 h after ingestion. However, carnosine was
undetectable in the plasma unless precautions were taken to inhibit blood
carnosinase activity ex vivo during and after blood collection. 3. The
amount of carnosine recovered in urine varied substantially between
subjects. It correlated negatively with carnosinase enzymic activity in the
plasma. Highest carnosinase activities were observed in those subjects who
regularly underwent physical training. 4. Urinary recovery of the
disaccharide lactulose also varied considerably between subjects, but was
substantially lower than that of carnosine. There was no significant
correlation between the recoveries of carnosine and lactulose. 5. When
lactulose was ingested with a hypertonic solution, the urinary recovery of
lactulose was generally increased. When carnosine was ingested with a
hypertonic solution, the urinary recovery of carnosine was reduced: hence
the paracellular route probably is not dominant for absorption of intact
carnosine. 6. Intact carnosine must have crossed the intestine to an extent
much greater than hitherto recognized. Rapid post-absorptive hydrolysis is a
severe obstacle to quantification of intact peptide absorption.
PMID: 1910085, UI: 91374363

Clin Chim Acta 1991 Feb 15;196(2-3):193-205
Purification and properties of human serum carnosinase.
Jackson MC, Kucera CM, Lenney JF
Pharmacology Department, School of Medicine, University of Hawaii, Honolulu

Carnosinase from human plasma was purified 18,000-fold to apparent
homogeneity in a four step procedure. The dipeptidase was partially
inactivated during DEAE-cellulose chromatography; however, it reactivated
slowly when concentrated and stored at 4 degrees C. In the second
purification step, hydroxylapatite column chromatography, two forms of the
enzyme were separated from one another. Human serum carnosinase was found to
be a glycoprotein with a pI of 4.4 and a subunit Mr of 75,000; the active
enzyme was a dimer, the two subunits being connected by one or more
disulfide bonds. The enzyme was especially active in hydrolyzing carnosine
and anserine, preferring dipeptides with histidine in the C-terminal
position. In most human tissues, the concentration of serum carnosinase was
proportional to the percentage of trapped blood in the sample. However, the
brain contained about 9 times more enzyme than expected, based on the amount
of trapped blood present. The physiological function of this enzyme seems to
be the hydrolysis of homocarnosine in the brain and the splitting of
carnosine and anserine in the blood stream. Six higher primates were found
to have serum carnosinase. Twelve nonprimate mammals were tested; all were
lacking the serum enzyme except for the Golden hamster, which had very high
concentrations of a carnosinase having somewhat different properties than
the higher primate enzyme.
PMID: 1903095, UI: 91230776

J Ment Defic Res 1985 Dec;29 ( Pt 4):383-9
Serum carnosinase deficiency: a non-disabling phenotype?
Cohen M, Hartlage PL, Krawiecki N, Roesel RA, Carter AL, Hommes FA

Serum carnosinase deficiency (McKusick 21220) is a rare condition, described
in 13 cases. Ten additional individuals with serum carnosinase deficiency
have been identified. All continued to excrete increased amounts of
carnosine in their urine despite a meat-free diet for 3 days. Serum
carnosinase activity ranged from 0-30% of normal. In four individuals a
normal Km for carnosine of 0.12 mM was observed, while in five individuals
an increased Km was found. Homocarnosine levels in CSF in three individuals
ranged from 3.4 to 15 mM. Clinical symptoms in these individuals were as
follows: attention deficit disorder: 4; non progressive developmental delay:
1; neurofibromatosis: 1; absences seizures: 1; severe, but non-progressive
mental retardation, seizures and neurosensory hearing loss: 1; progressive
childhood dementia; 1; clinically normal: 1. There was no correlation
between severity and type of the neurological symptoms and residual serum
carnosinase activity. Although a definite conclusion can only be made after
a considerably higher number of individuals has been analyzed, the suspicion
that serum carnosinase deficiency is unrelated to the neurological symptoms
is strengthened by these observations. There may, however, be an association
with a predisposition for mental deficiency.
PMID: 4093964, UI: 86143781 -- Tom ]

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