''N''-Acetylcarnosine (NAC) (Not to confuse with

N-Acetylcysteine Acetylcysteine, also known as ''N''-acetylcysteine (NAC), is a medication that is used to treat paracetamol overdose and to loosen thick mucus in individuals with chronic bronchopulmonary disorders like pneumonia and bronchitis. It has been used ...

) is a naturally occurring

compound Compound may refer to: Architecture and built environments * Compound (enclosure), a cluster of buildings having a shared purpose, usually inside a fence or wall ** Compound (fortification), a version of the above fortified with defensive struc ...

chemically related to the dipeptide

carnosine Carnosine (''beta''-alanyl-L-histidine) is a dipeptide molecule, made up of the amino acids beta-alanine and histidine. It is highly concentrated in muscle and brain tissues. Carnosine was discovered by Russian chemist Vladimir Gulevich. Ca ...

. The NAC molecular structure is identical to carnosine with the exception that it carries an additional acetyl group. The acetylation makes NAC more resistant to degradation by carnosinase, an

enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products ...

that breaks down carnosine to its constituent

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha a ...

s, beta-alanine and

histidine Histidine (symbol His or H) is an essential amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated –NH3+ form under biological conditions), a carboxylic acid group (which is in the d ...

Actions

Carnosine and metabolic derivatives of carnosine, including NAC, are found in a variety of tissues but particularly

muscle tissue Muscle tissue (or muscular tissue) is soft tissue that makes up the different types of muscles in most animals, and give the ability of muscles to contract. Muscle tissue is formed during embryonic development, in a process known as myogenesis. ...

. These compounds have varying degrees of activity as free radical scavengers. It has been suggested that NAC is particularly active against lipid peroxidation in the different parts of the

lens A lens is a transmissive optical device which focuses or disperses a light beam by means of refraction. A simple lens consists of a single piece of transparent material, while a compound lens consists of several simple lenses (''elements ...

in the eye. It is an ingredient in eye drops that are marketed as a dietary supplement (not a drug) and have been promoted for the prevention and treatment of

cataract A cataract is a cloudy area in the lens of the eye that leads to a decrease in vision. Cataracts often develop slowly and can affect one or both eyes. Symptoms may include faded colors, blurry or double vision, halos around light, trouble ...

s. There is scant evidence on its safety, and no convincing evidence that the compound has any effect on ocular health.

Research

Most of the clinical research on NAC has been conducted by Mark Babizhayev of the US-based company Innovative Vision Products (IVP), which markets NAC treatments. During early experiments performed at the Moscow Helmholtz Research Institute for Eye Diseases, it was shown that NAC (1% concentration), was able to pass from the

cornea The cornea is the transparent front part of the eye that covers the iris, pupil, and anterior chamber. Along with the anterior chamber and lens, the cornea refracts light, accounting for approximately two-thirds of the eye's total optical ...

to the

aqueous humour The aqueous humour is a transparent water-like fluid similar to plasma, but containing low protein concentrations. It is secreted from the ciliary body, a structure supporting the lens of the eyeball. It fills both the anterior and the poster ...

after about 15 to 30 minutes. In a 2004 trial of 90 canine eyes with cataracts, NAC was reported to have performed better than placebo in positively affecting lens clarity. An early human study NAC reported that NAC was effective in improving vision in cataract patients and reduced the appearance of cataract. The Babizhayev group later published a

placebo A placebo ( ) is a substance or treatment which is designed to have no therapeutic value. Common placebos include inert tablets (like sugar pills), inert injections (like saline), sham surgery, and other procedures. In general, placebos can af ...

-controlled

clinical trial Clinical trials are prospective biomedical or behavioral research studies on human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel vaccines, drugs, diet ...

of NAC in 76 human eyes with mild to advanced cataracts and reported similar positive results for NAC. However, a 2007

scientific review A review article is an article that summarizes the current state of understanding on a topic within a certain discipline. A review article is generally considered a secondary source since it may analyze and discuss the method and conclusions i ...

of the current literature discussed the limitations of the clinical trial, noting that the study had low statistical power, a high dropout rate and "insufficient baseline measurement to compare the effect of NAC", concluding that "a separate larger trial is needed to justify the benefit of long-term NAC therapy". Babizhayev and colleagues published a further human clinical trial in 2009. They reported positive results for NAC as well as arguing "only certain formulas designed by IVP... are efficacious in the prevention and treatment of senile cataract for long-term use."

Commentary

The

Royal College of Ophthalmologists The Royal College of Ophthalmologists, founded in 1988, is an independent professional body and one of the Medical Royal Colleges. They set the standards and examinations for medical doctors aiming to become ophthalmologists, and provide surgical ...

remains very skeptical about claims of efficacy in cataract reversal. It issued the following public statement about NAC in August 2008:

The evidence for the effectiveness of N-acetyl carnosine eye drops is based on experience on a small number of cases carried out by a Russian research team abizhayev To date, the research has not been corroborated and the results replicated by others. The long-term effect is unknown. Unfortunately, the evidence to date does not support the 'promising potential' of this drug in cataract reversal. More robust data from well conducted clinical trials on adequate sample sizes will be required to support these claims of efficacy. Furthermore, we do not feel the evidence base for the safety is in any way sufficient to recommend its use in the short term. More research is needed.

In a 2010 book on ocular disease, the current state of this subject is summarized as follows:

Carnosine (β-alanyl-L-histidine), and its topical prodrug formulation ''N''-acetylcarnosine (NAC), is advertised (especially on the internet) to treat a range of ophthalmic disorders associated with oxidative stress, including age-related and diabetic cataracts. No convincing animal studies or masked clinical trials have been reported.

A Cochrane review summarizing research up to June 2016 has concluded that there is "no convincing evidence that NAC reverses cataract, nor prevents progression of cataract". The authors did not include the studies conducted by the Babizhayev group because they were unable to establish that the research used scientific methods appropriate for

References

{{reflist Cochrane Database Syst Rev. 2017 Feb 28;2:CD009493. doi: 10.1002/14651858.CD009493.pub2. Dipeptides Acetamides