Carnosine, the new anti-aging supplement 
  by Marios Kyriazis MD

Although carnosine (also known as L-carnosine) has been known for about a century, its antiaging properties have only been extensively studied during the past few years.  A recent literature review revealed over 780 published studies on carnosine, mainly by Russian and Japanese researchers.  However, more widespread interest in this natural nontoxic product has only recently been increased, fuelled by dramatic Australian and British discoveries about its antiaging actions. (1)            to order

Carnosine (B-alanyl-L-histidine) is a naturally-occurring di-peptide (a combination of two amino acids), found in muscle, brain and other innervated animal and human tissues.  It is formed by a process involving the enzyme   carnosine-synthetase which bonds the amino acids alinine and histidine. This process occurs mainly in muscles and brain.  It is kept in equilibrium by the carnisinases which are enzymes specifically aimed at inactivating carnosine in the tissues or in the blood.   
                           carnosine autism research

There are several other related dipeptides such as carcinine, anserrine, homocarnosine and ophidine, all of which are naturally-occurring.  These are believed to be buffering agents, helping to maintain the homeostatic equilibrium. (2)

High concentrations of carnosine are present in long-lived cells (such as in neuronal tissues).  The concentration of carnosine in muscles correlates with maximum lifespan, a fact that makes it a promising bio-marker of aging.  It is high in actively contracting muscles and low in cases of muscular disease such as Duchennes's muscular dystrophy.  Its concentration in mammalian muscles possibly decreases with age, a fact which strengthens the case for supplementation. 

In cases of cataract in animals, carnosine concentration in the lens was found to be low. The lower the concentration of carnosine, the higher the severity of cataract.  Rabbits fed on a high cholesterol diet, were found to be well protected against atherosclerosis and cataract if given carnosine supplements.  In another experiment, dogs were also found to be protected against cataract if given carnosine supplements. (2)

Antioxidant Properties
Carnosine is widely believed to he an antioxidant which stabilizes and protects the cell membrane. Specifically, as a water-soluble free radical scavenger it prevents lipid peroxidation within the cell membrane (3).  It is thought to be a natural counterpart to lipid-soluble antioxidants such as vitamin E.  Maybe it is not a coincidence that carnosine increases vitamin E levels in rats. 

Many antioxidants are aimed at preventing free radicals from entering the tissues, but have no effect after this first line of defense is broken.  Carnosine is not only effective in prevention, but it is also active after free radicals react to form other dangerous compounds.  So, it protects the tissues from these damaging 'second-wave' chemicals.  For example, a highly reactive lipid peroxidation end-product called malondialdegyde (MDA)- a deleterious product of a free radical reaction- is blocked by carnosine. (4,5)  MDA, if left uncontrolled, can cause damage to lipids, enzymes and DNA, and plays a part in the process of atherosclerosis, joint inflammation, cataract formation, and aging in general.  Carnosine, by reacting and inactivating MDA, sacrifices itself in order to protect the amino acids on the protein molecule.  

Other Benefits
Carnosine plays a part in neurotransmission, it is a heavy metal binder (chelates ionic metals) and modulates enzymatic activities.  Other actions, some of which are not extensively studied include: 

* anti-neoplastic properties, which make it a potentially beneficial agent for use in cancer prevention. 

* immune booster (it stimulates maturation of immunocompetent cells), and reduces inflammation. 

* wound healing properties and protection against radiation damage (both preventing damage and reversing the post-radiation syndrome).   Laboratory animals treated with carnosine were found to have faster and better wound healing rates compared to controls. This has potential applications to treating burns, wounds following surgery, or during nutritional preparation for surgery. (5)

* a reduction of gastric ulceration (particularly when the ulcer is related to stress), both by preventing the formation of the ulcer and by healing it (carnosine increases the formation of granulation tissue).  It does not affect acid secretion.

Glycosylation
Perhaps, the most important action of carnosine is its anti-glycosylation effect. (8)  One of the cardinal processes of aging, apart from free-radical damage, is the process of glycosylation (or glycation).  During normal, everyday metabolism, sugar aldehydes may react with the amino acids on the protein molecule.  The result is the formation of AGEs (Advance Glycosylation End-products). These are abnormal, cross-linked. oxidized products which are thought to cause extensive damage to the organism. Carnosine blocks this deleterious reaction. protecting against cross-linking of proteins, cross-linking of proteins to DNA molecules, and formation of other abnormal proteins, all of which are fundamental features of the aging process. 

Other anti-glycators such as aminoguanidine may also protect against glycosylation hut not as effectively as carnosine. Some amino acids (arginine or lysine) are also able to combine with glucose in order to eliminate dangerous AGEs, but the end-product of this reaction is mutagenic (i.e. it may cause cancer).  The combination of carnosine with glucose however is not mutagenic.  

Specifically, carnosine reacts with and inactivates aldehydes and ketones. reducing protein glycosylation and the formation of AGEs. It also binds to already formed AGEs and inactivates them. Normally, AGEs are removed by scavenging macrophages (immune system cells) which carry special receptors called RAGEs. Carnosine facilitates this process of elimination, by helping macrophages to better recognize the AGE molecule. Because of its anti-glycosylation actions, carnosine may be useful in treating or preventing diabetic complications such as cataract, neuropathy and kidney failure. 

Amyloid Protection
In experiments, treatment with carnosine was found to reduce or completely prevent cell damage caused by beta amyloid (9), the substance found in the brain of Alzheimer's disease patients.  Beta amyloid can interact with certain RAGE receptors causing damage to the nerves and arteries of the brain. Carnosine blocks and inactivates beta amyloid, so it protects neural tissues against diseases such as dementia. 

There have been some concerns regarding carnosine's ability to form lipofuscin (the age pigment commonly found in the aging brain and in other tissues).  Lipofuscin is merely a sign that other deleterious reactions have already taken place.  For example; free radicals and toxic aldehydes may react with valuable proteins as described above, and cause damage, leaving lipofuscin as a left-over product.   One way to save the protein molecule is to use carnosine instead.  Carnosine actively and swiftly binds to aldehydes before these are able to cause any damage. The end-result of this reaction may also be inactive lipofuscin compounds. 

In this case, lipofuscin is formed not by wasting  valuable protein material but by using sacrificial carnosine, leaving the proteins free to function properly.  Lipofuscin, however formed, is thought to be generally inactive to normally everyday situations. High amounts of free radicals and toxin in the organism are best inactivated by using supplementary carnosine than tissue protein.  Of course, it would be best to reduce the exposure to too many free radicals in the first place. This can be achieved for example, by avoiding pollution, cigarette smoking, sedentary life, and unsuitable nutrition. 

Use on Humans
After dozens of reports about carnosine's antiaging actions in laboratory experiments, the next logical step was to start using it on humans, specifically for antiaging purposes.  Carnosine supplements have been used in the past by body-builders, athletes and others, but its use has been confined mainly for improving muscular fatigue, and not for longevity.

Recently, eye drops containing carnosine have been developed and used by Russian researchers. (10)  The drops were found to be effective in treating human corneal erosions and other corneal diseases. For example, carnosine drops accelerate the healing of ulcers in herpes and bacterial infections of the eye. 

During a preliminary experiment designed specifically for antiaging (11), I used L-carnosine supplements (50 rng daily) on 20 healthy human volunteers, aged 40-75 years, for a period of 1-4 months. No side affects were reported.  Five users noticed significant improvements in their facial appearance (firmer facial muscles), muscular stamina and general well-being.  Five others reported possible benefits, for example better sleep patterns, improved clarity of thought and increased libido. The rest did not report any noticeable effects.  This is not surprising because supplementation with carnosine is not expected to show any significant noticeable benefits in a short time, but it should be used as an insurance against deleterious effects of the aging process.  If any benefits are noted, these should be considered as an added extra bonus.   It is worthwhile persevering with the supplementation long term, even if you do not experience any obvious benefits, as you will still be well protected against aging.

Carnosine can be used together with vitamin E and/or Co-enzyme Q10 for full antioxidant protection, but even if it is used on its own it should still confer significant protection both against free radicals and against glycosylation. 

Indeed, the carnosine preparation I used in my experiments contains also 30 IU of vitamin E as standard.  Some people prefer to use 100 mg of carnosine a day (i.e. double the initial standard dose) and they find that there are still no side effects.  Foodstuffs containing dietary carnosine are lean red meat and chicken.  

Conclusion
Where do we go from here?  Further experiments are in progress, aimed at examining more widely the effects of carnosine on human aging. Those who want to he at the forefront of innovative antiaging medicine should he taking carnosine now. It is expected that carnosine supplementation will become much more widespread during the next five years, making carnosine as popular as vitamin E is today.

References
1) Hipkiss A. Carnosine. a protective, anti-ageing peptide? Int J Biochem Cell Biol. 1998, 30: S63-868.

2) Quinn PL Boldyrev AA. Formaziuk VH. Carnosine: its properties, functions and potential therapeutic applications. Mol Aspects Mod, 1992, 13(5):379-444.

3) Tarnha M, et al. Hydroxyl radical scavenging by carnosine and Cu(ii)-carm)sine complexes. Int J Radial Biol, 1999 75(9):1 177-1188. 4) Hipkiss A. et al. Protective effects of carnosine against MDA-induced toxicity towards cultured rat brain endothelial cells. Neuroscience Letters. 1997. 135-138.

5) Hipkiss A et al. Protective effects of carnosine against protein modification mediated by nialondialdchyde and hypochlorite. Bioch Biophys Acta 1998, 1380;46-54.

6) Roberts PR, Black KW, Santamauro JT. Dietary peptides improve wound healing following surgery. Nutrition, 1998, 14(3):26h-2^9.

7) McFarlandGA,HollidayR. Further evidence for the rejuvenating effects of the dipeptide I .-carnosine on cultured human diploid fibroblast. Exp Gerontol 1999 34(l):35-45.

8) Hipkiss A, Ghana 14. Carnosine protects proteins against rnelhyiglyoxal-mediated modicatiations. Biochem Biophys Rcs Goinm 1998. 248 (1); 28-32.

9) Preston J et al. Toxic effects of B-amyloid on immortalised rat brain endothelial cell: protection by carnosine, homocarnosine and B-alanine. Neuroscience letters 1998, 242; 105-108.

10) Maichuk luF, Formaziuk VF. Sergienku VI. Development of carnosine eye drops and assessing their efficiency in corneal diseases. Vestn Oftalmol 1997.1 13(ft);27-31.

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Dr. Marios Kyriazis is considered to be an expert on carnosine and has been actively involved in its research over the last few years.

We are sometimes asked why we don’t suggest high doses of Carnosine; well over and above the 50-150mg per day recommended. It has been suggested that only mega doses of Carnosine (i.e. 1000mg+ ) can avoid degradation by carnisinases and that only mega dosages get results. Dr. Kyriazis answered this very question. Dr. Kyriazis joins with the other scientists behind Carnosine, including Dr. Hipkiss who believe that some of the benefits of carnosine are derived AFTER carnosine has been degraded by carnisinases to produce histidine and alanine, therefore degradation may be a good thing.

Dr. Kyriazis has conducted a trial with Carnosine to show that even low dosages are effective.

Carnosine can reduce urinary MDA concentration
    By Marios Kyriazis, MD

Introduction

MDA (Malondialdehyde) is a free radical produced during lipid peroxidation and can contribute to protein modification (or cross-linking). Carnosine is believed to protect against MDA-induced damage. In this paper, this premise is used to help establish an ideal dose of Carnosine for anti-aging purposes in humans.

Patients and Methods

Twelve healthy volunteers (5 males, 7 females) aged 40-75 took part in this study. Oral carnosine  was introduced and withdrawn at weekly intervals and at variable doses. The results were studied using the Free Radical Test Kit (Vespro Limited) which measures urinary MDA using a colorimetric method. The subjects varied their Carnosine intake at weekly intervals but continued using their existing supplements uninterrupted throughout the trial period.

Results

These are shown in Figure 1. Dosages as low as 50mg of Carnosine were found to be effective in reducing urinary MDA concentration. There is a wide variation in values but a clearer picture becomes evident from studying the mean values. These show a decline in urinary MDA with increasing Carnosine dosage.

Figure One

Discussion

The study is limited by the small numbers of subjects and by the difficulty in establishing exact values of MDA, however two conclusions appear clear:

1.    The assertion that at least 1000mg of Carnosine needs to be taken daily in order to by-pass Carnosine degradation does not seem to hold true on this occasion.

2.   The ideal dose of Carnosine seems to be around 100mg to 200mg daily, preferably taken in association with other anti-oxidants.

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Double-Blind, placebo-controlled Study of L-carnosine supplementation in children with autistic spectrum disorder

Michael G. Chez, M.D., Cathleen P. Buchanan, Ph.D.,
Jamie L. Komen, M.A., Marina Becker, R.N.

Objective: L-Carnosine is an amino acid dipeptide that may enhance frontal lobe function.  We therefore sought to investigate whether L-Carnosine supplementation for children with Autistic Spectrum Disorders (ASD) results in observable, objective changes in language and/or behavior in contrast to placebo. 

Design/Methods: Thirty-one children (21 M, mean age= 7.45; range = 3.2-12.5 yrs )meeting inclusion criteria were enrolled in an 8 week blinded trial of either 400 mg BID powdered L-Carnosine or placebo. Children were assessed at a pediatric neurology clinic with the Childhood Autism Rating Scale (CARS), the Gilliam Autism Rating Scale (GARS), the Expressive and Receptive One-Word Picture Vocabulary tests (E/ROWPVT), and biweekly parental Clinical Global Impression of Change (CGI), at baseline and 8 week endpoint.

Results: Children who were on placebo (n=17) did not show statistically significant changes on any of the outcome measures. After 8 weeks on L-Carnosine, children (n=14) showed statistically significant improvements on the GARS total score, GARS Behavior, Socialization, and Communication subscales, and the ROWPVT (all p’s<.05). EOWPVT and CARS showed trends in improvements, which were supported by parental CGI.

Conclusions: Oral supplementation with L-Carnosine resulted in demonstrable improvements in autistic behaviors as well as increases in language comprehension that reached statistical significance.  Although the mechanism of action of the amino acid is not well understood, it is believed that it acts to modulate neurotransmission and affect metal ion transfer of zinc and copper in the entorhinal cortex. This may enhance neurological function or act in a neuroprotective fashion.

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Carnosine A Remarkable Multipurpose Anti-Aging Nutrient
  by Daniel Bourassa, D.C.

Carnosine (beta-alanyl-L-histidine) is a naturally-occurring dipeptide that was discovered in Russia in 1900.  Because much of the research with carnosine was performed in Russia, it has been largely unavailable to Western scientists until recently.  Carnosine, not to be confused with L-carnitine, is now becoming increasingly recognized for its tremendous potential as a highly effective anti-aging nutrient. Carnosine contains the amino acids alanine and histidine, and is found in highest concentrations in long-lived tissues such as skeletal muscle, cardiac muscle and brain (Jackson and Lenney 1996), and has antioxidant, buffering, free radical scavenging and even neurotransmitter properties. 

Carnosine Declines with Age 

Stuerenburg and Kunze (1999) report that in human subjects with neuromuscular disease, muscle concentrations of carnosine decline 63% from age 10 to 70. These authors report that with increasing age, the antioxidant effect of carnosine decreases by half. This marked reduction in muscle carnosine concentration may be a cause of the age-related decline in muscle mass, strength and function. Stress and trauma also cause a reduction in carnosine levels, which may help explain the increased mortality in the elderly following stressful events.  

Carnosine's Multiple Anti-aging Mechanisms 

This illustrates several biological roles in which carnosine participates, including methylation (giving rise to anserine or ophidine), hydrolysis (leading to histidine and beta-alanine), and decarboxylation (resulting in histamine formation, which interacts with beta-alanine to result in the formation of carnicine). Carnicine, a stable analog of carnosine, has been used experimentally to reverse cataracts.  Carnosine's two amino acids, histidine and alanine, are metabolized in the citric acid cycle.  Alanine enters through the Co-enzyme A pathway and histidine through (alpha)-ketoglutarate pathway.  

Aging is associated with damage to cellular proteins, resulting in inter- and intra-molecular cross-linking. Carnosine protects cellular proteins from such metabolic damage in at least two ways. First, as an antioxidant, carnosine prevents the formation of oxidized sugars, or glycosyl radicals, also called advanced glycosylation end-products (AGEs) (Hipkiss, et al, 1998).  Second, carnosine bonds with potentially harmful carbonyl groups that attack and bind with proteins imbedded in the cellular membrane, and neutralizes them. Both of these processes have important implications for anti-aging therapy, in that carnosine not only prevents damaging cross-links from forming, it eliminates cross-links that have previously formed, thus restoring normal membrane function (Hipkiss and Brownson, 2000).  

Therapeutic Uses for Carnosine 

A wide range of therapeutic uses have been proposed for this remarkable substance (Table I). As early as 1935, carnosine was recognized as a treatment for polyarthritis. Carnosine has the remarkable ability to down-regulate cellular and enzymatic processes when in excess, and up-regulate them when suppressed.  For example, carnosine decreases platelet aggregation in patients with abnormal clotting tendencies ("thins the blood"), and increases platelet aggregation in patients with low clotting indices (Nititenko, et.al., 1995). 

Closely related to this auto-regulation ability are carnosine's effects on anti-inflammatory and immunoregulatory processes.  Carnosine suppresses excess immunoreaction in immature mice, and stimulates immunoreaction in aged mice.  Carnosine activates both B and T lymphocytes (Nagai and Suda, 1986).  Carnosine increased the respiratory burst and interleukin-1 beta production of human neutrophils (Tan and Candlish, 1998,) indicating an important up-regulation of the immune response.  Carnosine also has protective effects on blood cell membranes, enhancing their survival, and has demonstrated cell membrane-stabilizing effects, offering protection against chemical-induced hemolytic anemia (Nagai, et al., 1990) 

Table I: Therapeutic uses for carnosine

       Therapeutic Effects                             Time of Discovery

Carnosine for Vision 

Carnosine-containing eye drops have demonstrated efficacy in treating a variety of ophthalmic conditions, including corneal diseases, cataracts, as well as glaucoma and increased intraocular pressure.  In 1997, clinical trials were conducted on 109 ophthalmic patients with carnosine-containing eye drops. The results confirmed accelerated healing of corneal erosions, trophic keratitis, post-herpetic epitheliopathy, primary and secondary corneal dystrophy, and bullous keratopathy (Maichuk et. al., 1997). Most striking, however, was the ability of carnosine to eliminate existing cataracts (Yuneva, et. al., 1999).  Carnosine actually restores the proteins in the lens by removing the carbonyl groups, as described earlier.   Furthermore, carnosine is thought to function as a "molecular water pump" (Baslow, 1998).  In earlier experiments it was demonstrated that applying carnosine to the conjunctiva (the membrane covering the eye) caused a decrease in normal intraocular pressure and reduced prostaglandin-induced ocular hypertension (related to glaucoma).  

Enhanced Healing and Anti-Ulcer Effects of Carnosine 

Carnosine also accelerates wound healing, modulates immune responses, and increases immunocompetence (Nagai and Suda, 1988).  As far back as 1936, carnosine was found to be of help in the treatment and prevention of gastric ulcers.  In a more recent study, oral carnosine significantly inhibited erosions in both the stomach and duodenum (Truitsina, et. al., 1997).  Those with gastric and duodenal ulcers thus might benefit from supplementing with this amazing dipeptide.  

Visible Anti-aging Benefits  

In a recent article Dr Marios Kyriazis reported that his patients who take carnosine supplements often receive comments that they simply look younger.  This may be a reflection of the phenomenon observed in 'in vitro' experiments which show that carnosine actually rejuvenates older cells in culture (McFarland and Holliday, 1994), and 'in vivo' animal experiments in which carnosine prevented the development of visible features of aging (Boldyrev, et. al., 1999).  In that study, carnosine significantly delayed the appearance of skin ulcers, periopthalmic lesions, spinal lordokyphosis and behavioral responses such as activity and passive avoidance (all characteristic of aged animals). In another recent article, Russian scientists reported that not only did the carnosine-fed SAMP1 mice appear much more youthful than controls, but experienced a 20% increase in lifespan (Yuneva, et al, 1999).  

Conclusion 

Carnosine is generally considered an extremely non-toxic and safe substance. Boldyrev and other authors have reported that absorption of carnosine is excellent, perhaps greater than 70%. As with other antioxidants, carnosine acts synergistically when taken with other antioxidants. (For example, when vitamin E was taken with carnosine, levels of both substances were higher in cardiac muscle than when either was taken alone.)  

Dr. Kyzarias, recommends 50–100 mg/day to his patients. He reports that noticeable benefits have been reported at this intake level. He also indicated that these levels were felt to be adequate by Alan Hipkiss, a top British and world researcher on carnosine at the University of London.  

References:

1. Baslow, MH. Function of the N-acetyl-L-histidine system in the vertebrate eye. Evidence in support of a role as a molecular water pump. J Mol Neurosci, 1998, 10(3), 193-208. 

2. Boldyrev, AA, Gallant, SC, Suhkich, GT. Carnosine, the protective, anti-aging peptide. Biosci Rep, 1999, 19 (6), 581-7. 

3. Gariballa, SE, Sinclair, AJ. Carnosine: physiological properties and therapeutic potential. Age and Aging, 2000, 29: 207-210. 

4. Hipkiss, AR, Brownson, C. A possible new role for the anti-aging peptide carnosine. Cell Mol Life Sci, 2000, 57 (5): 747-53. 

5. Hipkiss, AR, Preston, JE, Himsworth, DT, Worthington, VC, Keown, M, Michaelis, J, Lawrence, J, Mateen, A, Allende, L, Eagles, PA, Abbott, NJ. Pluripotent protective effects of carnosine, a naturally occuring dipeptide. Ann N Y Acad Sci, 1998, 854:37-53. 

6. Hipkiss AR. Carnosine, a protective, anti-aging peptide? Int J biochem Cell Biol, 1998, 30(8): 863-8. 

7. Jackson, MC, Lenney, JF. The distribution of carnosine and related dipeptides in rat and human tissues. Inflamm Res 1996, 45(3): 132-5. 

8. Lehninger, AL. Principles of Biochemistry; 1982 Worth Publishers; (p321). 

9. Maichuk, IUF, Formaziuk, VE, Sergienko, VI. Development of carnosine eyedrops and assessing their efficacy in corneal diseases. Vestn Oftalmol, 1997, 113(6): 27-31. 

10. McFarland, GA, Holliday, R. Retardation of the senescence of cultured human diploid fibroblasts by carnosine. Exp Cell Res, 1994, 212(2): 167-75. 

11. Nagai K, Suda T, Kawasaki K, Yamaguchi Y. Effects of L-carnosine on blood cells and biomembrane. Nippon Seirigaku Zasshi, 1990, 52(10): 339-44. 

12. Nagai K, Suda T. Immuno-enhancing actions of carnosine and homocarnosine. Nippon Seirigaku Zasshi, 1986, 48 (11):735-40. 

13. Nagai k, Suda T; Realization of spontaneous healing function by carnosine. Methods Find Exp Clin Pharmocol, 1988, 10(8): 497-507. 

14. Nikitenko Niu, Shavratskii VKh, Boldyrev AA, Suslina ZA, Ionova VG; Effect of carnosine and its derivatives on ADP-induced human platelet aggregation. Vopr Med Khim, 1995, 41(1): 41-3. 

15. Stuerenburg HJ, Kunze K; Concentrations of free carnosine (a putative membrane-protective antioxidant) in human muscle Biopsies and rat muscles. Archives of Gerontology and Geriatrics, 1999, 29: 107-113.

16. Tan KM, Candlish JK. Carnosine and anserine as modulators of neutrophil function. Clin Lab Haematol, 1998, 20(4): 239-44. 

17. Truitsina, IE, Shabanova, M, Chikunova, BZ, Shavratskii, Vkh, Formaziuk, VE, Sergienko, VI, Stvolinskii, SL, Boldyrev, AA. Characterization of the anti-ulcer effectiveness of carnosine. Patol Fiziol Eksp Ter, 1997, 4: 17-20. 

18. Yuneva, M.O., Bulygina, E.R., Gallant, S.C., et al. Effect of carnosine on age-induced changes in senescence-accelerated mice. J Anti-Aging Medicine, 2: 1999, 337-342.  

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Double-Blind, placebo-controlled Study of L-carnosine supplementation in children with autistic spectrum disorder

Michael G. Chez, M.D., Cathleen P. Buchanan, Ph.D.,
Jamie L. Komen, M.A., Marina Becker, R.N.

Objective: L-Carnosine is an amino acid dipeptide that may enhance frontal lobe function.  We therefore sought to investigate whether L-Carnosine supplementation for children with Autistic Spectrum Disorders (ASD) results in observable, objective changes in language and/or behavior in contrast to placebo. 

Design/Methods: Thirty-one children (21 M, mean age= 7.45; range = 3.2-12.5 yrs )meeting inclusion criteria were enrolled in an 8 week blinded trial of either 400 mg BID powdered L-Carnosine or placebo. Children were assessed at a pediatric neurology clinic with the Childhood Autism Rating Scale (CARS), the Gilliam Autism Rating Scale (GARS), the Expressive and Receptive One-Word Picture Vocabulary tests (E/ROWPVT), and biweekly parental Clinical Global Impression of Change (CGI), at baseline and 8 week endpoint.

Results: Children who were on placebo (n=17) did not show statistically significant changes on any of the outcome measures. After 8 weeks on L-Carnosine, children (n=14) showed statistically significant improvements on the GARS total score, GARS Behavior, Socialization, and Communication subscales, and the ROWPVT (all p’s<.05). EOWPVT and CARS showed trends in improvements, which were supported by parental CGI.

Conclusions: Oral supplementation with L-Carnosine resulted in demonstrable improvements in autistic behaviors as well as increases in language comprehension that reached statistical significance.  Although the mechanism of action of the amino acid is not well understood, it is believed that it acts to modulate neurotransmission and affect metal ion transfer of zinc and copper in the entorhinal cortex. This may enhance neurological function or act in a neuroprotective fashion.