Carnosine Toxicity?

[Guest guest]

" Mambo Mambo " <mambomambo@...> wrote:

> There was some bad PR about Carnosine a few weeks back.

> I'll post it and

> would love comments from you, Bob and anyone else who is

> interested.

> The studies described were performed on cell culture

> experiments, i.e.

> cells grown in bottles away from a living being, or in

> rodents.

No basic biochemical research is being done on humans for ethical

reasons. The normal policy is to utilize in-vitro studies (which are the

least expensive) and confirm any positive results with animal studies.

Only the very best results are confirmed in humans, usually after

significant delay due to the cost of human studies and only when a

compensatory benefit (health or economic) is expected. There is no point

in prospective tests of life-extending chemicals or interventions in

humans or any other long-lived species. By the time enough subjects die

to test the hypothesis, both the investigators and the public that

expected to benefit may have died as well.

It is only after one characterizes the mechanisms by which a positive or

negative effect occurs that one can say whether an in-vitro or a murine

result is relevant to humans. The in-vitro carnosine research was

questionable until both murine and human studies showed that it was

possible to achieve the tested plasma and tissue levels of carnosine by

oral administration. That retroactively validated most of the in-vitro

research. The mechanisms by which carnosine has been shown to function

in both the in-vitro and murine studies are present in humans and do

function similarly.

> " carnosinemia, an inherited condition, transmitted as an

> autosomal recessive

> trait, that is characterized by the presence of excessive

> amounts of

> carnosine in the blood and urine. Caused by genetic

> deficiency of the enzyme

> carnosinase (aminoacyl-histidine dipeptidase),

A similar argument would put everyone on a PKU diet because a small

minority are genetically unable to process phenylalanine. There are

genetic sensitivities to copper and iron as well. An excess of salt,

sugar or water can be fatal but that doesn't prove toxicity or disprove

benefit for any of those at normal levels. Carnosine toxicity has not

been seen in any mammal at intakes of grams per kilogram. One gram per

kilogram would be 70 grams for the average human. Against that, an

intake of 0.5-2.0 grams is entirely safe.

> " It is possible that the active molecule in the

> carbonyl/aldehyde

> binding in vivo is in fact histidine. ... Perhaps the

> natural toxicity

> of free histidine necessitates its storage as carnosine,

> and the

> presence of tissue and serum carnosinases liberate

> histidine only at

> specific locations and circumstances. "

I raised this possibility myself earlier. The body isn't very good at

storing or transporting individual free amino acids and might just use

carnosine as a histidine transporter. Except for the area of glycation

prevention, I've not seen pharmokinetic studies proving whether

carnosine or a metabolite is the active form. I've also seen no research

into the age-related decline in carnosine levels. Is the problem

decreased production vs. increased degradation? Is production limited by

availability of some cofactor or by the raw amino acids themselves

(especially histidine)? Only recently have researchers asked those

questions regarding glutathione.Were those questions answered

affirmatively one might be able to increase endogenous carnosine

production. Even so, carnosine supplementation might still considered a

cost-effective intervention.

Bob Cruder