NAC’s parent compound, carnosine, protects lens proteins from the harmful effects of cross-linking
By Hyla Cass, M.D.
If the eye is the window to the soul, as the old saying goes, then what does it say about our soul if our eyes become clouded by cataracts? Well, nothing—the soul is impervious to such minor problems as an inability to see. To the mind and body, however, this is a major problem, to put it mildly. And here, in contrast to some other aspects of human health, there is no possibility that a “mind-over-matter” approach will produce any improvement. If cataracts—the leading cause of blindness—are forming in your eyes, you cannot will them away. Only physical or chemical intervention can remedy the problem.
Physical intervention, of course, means surgery. Cataract surgery—the replacement of your natural lenses with synthetic ones—is among the most common operations performed throughout the world today; in the United States it is the most common operation, at about 1.5 million annually. In the hands of a skilled ophthalmic surgeon, the operation is usually quick and easy, and the success rate is very high.
From the patient’s point of view, cataract surgery is generally a breeze, as operations go. But its still an operation, with all that that entails: some inconvenience and discomfort, the need for postoperative recovery, including drugs, and the possibility of complications from the surgery or the drugs, or both. Not to mention the cost, whether out of pocket or in the form of insurance premiums that would be lower (OK, could be lower) if the surgery weren’t so common.
For all those reasons, you should avoid any kind of surgery if at all possible—while recognizing that a successful surgery is one of humankind’s greatest blessings (we have always had a love-hate relationship with surgery). “If at all possible” is the key phrase, of course, and the question of the day is: What is possible in the way of nonsurgical intervention for cataracts?
Prevent, and Supplement
As always, the best intervention is prevention. In this case, that means protecting your eyes from excessive long-term exposure to ultraviolet radiation (wear UV-blocking sunglasses!), eating a well-balanced diet that’s rich in fruits and veggies (many of which are loaded with beneficial antioxidants), getting plenty of exercise (good for every aspect of your health), not smoking (not smoking!), and not growing old.
Oops—that last one is a bit tricky. If you insist on growing old, or if you’re already there, do not despair. Although your risk for cataracts increases with advancing age, it’s never too late to adopt healthier lifestyle choices that can reduce that risk or slow down the progression of cataracts if they’re already forming. For starters, follow the advice given in the preceding paragraph. It will make you a healthier and happier person, even if you do get older. Next, consider the use of nutritional supplements (which are a chemical intervention because they consist of chemical compounds)—they can reduce the risk for, and mitigate the effects of, many kinds of age-related ailments, not just cataracts.
N-Acetylcarnosine Has Dual Benefits
Quite a few supplements are good for your eyes in one way or another, but one compound, N-acetylcarnosine, stands out for a special reason: not only can it help prevent cataract formation, but there is evidence to show that it can even treat the condition by reversing the formation of existing cataracts to some degree. Most of the research leading to this conclusion has been done in Russia, where N-acetylcarnosine’s parent compound, carnosine, was discovered a century ago (see the sidebar on carnosine). We reported on some of that research ("N-Acetylcarnosine May Help with Cataracts”).
Carnosine, a Curious Chemical Compound
Carnosine (from the Latin word for flesh) is found naturally in the heart and skeletal muscles. Its biological role is still mostly a mystery, but it’s believed to have antioxidant properties that help protect our cells from oxidative stress caused by free radicals. Oxidative stress is implicated in (among many other things) the chemical reactions that lead to the destructive, age-related cross-linking and aggregation of proteins.
Carnosine also chelates copper (i.e., it acts as a chemical scavenger for copper ions), and it activates myosin ATPase. Myosin, the most common protein in muscle cells, is responsible for the elastic and contractile properties of muscle. ATPase is an enzyme that catalyzes the conversion of ATP (adenosine triphosphate) to ADP (adenosine diphosphate). That last item may sounds like a ho-hummer until you realize that it’s the source of the chemical energy that powers most
cellular activity. The ATP-to-ADP conversion is involved in countless biochemical processes. In conjunction with myosin (where carnosine acts as an activator), it powers our muscles.
Carnosine is also found in nerve tissue and the brain, where it’s the dominant nitrogen-containing compound not derived from protein. All proteins consist of long chains of amino acids, and short chains of about 50 or fewer are called polypeptides, or just peptides. The smallest possible peptide, consisting of only two amino acids, is called a dipeptide, and that is what carnosine is—its two constituents are alanine and histidine.
Most dipeptides (and tripeptides, etc.) are derived from proteins, but carnosine is not—it’s synthesized independently of proteins. Another compound in this special category is glutathione, a tripeptide that is the body’s most abundant and most important antioxidant. Glutathione (which cannot be taken orally) is critical for protecting the lenses of our eyes from free radical damage. Numerous other antioxidants, notably lipoic acid (the “antioxidant’s antioxidant”) and vitamins C and E, are also beneficial, as are various bioflavonoids, carotenoids, and minerals (zinc and selenium in particular).
Carnosine is soluble in water but not in lipids (fats and fatty compounds), and therein lies a problem: it has a hard time getting through cell membranes, which are made of lipids, to gain access to the aqueous interior of our cells. However, its chemical derivative N-acetylcarnosine (NAC—not to be confused with N-acetylcysteine, which is also abbreviated NAC), is relatively soluble in lipids (and in water), so it can pass through our cell membranes more easily. Inside the cells, NAC is gradually broken down to carnosine, which then exerts its beneficial effects. A further advantage of NAC is that it’s immune to the carnosine-degrading enzyme carnosinase, which is present in extracellular fluid.
From Age to AGEs to Cataracts
Since NAC is administered topically to the eyes, it must diffuse first through the conjunctiva, then the cornea, and then the aqueous humor before it can reach the lens.* (The aqueous humor is a clear, watery liquid that carries nutrients for the cornea and the lens, both of which lack a blood supply so that they can be transparent). The cells of the lens are unique in that they’re the only cells in the human body that are never replaced through the normal process of death and renewal. Thus, any kind of damage to these cells that cannot be repaired by inborn cellular mechanisms will accumulate throughout your lifetime.
*When molecules diffuse into a cell, some will remain there, and some will diffuse through the cell and out the other side, where they can then diffuse into the adjacent cell, etc. (they can also diffuse through the gaps between cells). Thus the molecules’ concentration tends to diminish through successive layers of cells, so enough molecules must be applied to begin with to achieve the desired concentration in the target area—in this case, the lens.
And what kind of damage does occur? By far the most important kind, especially as the body ages, is the gradual formation of … AGEs. That’s not a joke—it stands for advanced glycation end products, a kind of cellular gunk that builds up in many different kinds of cells and degrades their function. The immediate cause is glycation, an undesirable chemical reaction between sugars and proteins. The proteins of interest here are of a special kind that occurs only in our lenses. They’re called crystallins, and in a healthy lens they’re beautifully ordered in such a way that, under the laws of physics, the lens will be transparent to light.
Under the influence of oxidative stress, however, such as that caused by ultraviolet radiation or other deleterious influences (among them, age), this molecular order—and with it, transparency of the lens—is degraded. As sugars react with crystallins to form molecular complexes, the crystallins become cross-linked with each other (this represents the advanced end product part of the process), forming the large aggregates called AGEs. As the AGEs grow in size and extent, the lens becomes cloudy, and you’ve got a cataract.
Can Carnosine Reverse the Opacity and Light Scattering of AGEs?
Now what? You see your ophthalmologist, naturally. The question is, will he or she want to treat your condition naturally, i.e., with nutritional supplements, or with drugs or surgery? That depends on many factors, of course, but if supplements are to be considered, the one of primary interest will be NAC—not just because of the positive results obtained by the Russian researchers in clinical trials with human cataract patients, but also because of laboratory studies confirming the actions of NAC’s parent compound, carnosine, on lens AGEs.
Recent research at the University of Health Sciences in Kansas City, Missouri, has shown that carnosine is able to “disaggregate” (break up) AGEs that are produced in the laboratory by chemical reactions similar to those that occur (over periods of months or years) in our lenses.1 The researchers synthesized AGEs by reacting methylglyoxal (an intermediate in glucose metabolism), with alpha-crystallin from cow lenses. They then measured the degree of opacity and the amount of light scattering in AGE samples with and without carnosine treatment, as well as in pure, nonaggregated (non-AGEd) alpha-crystallin.
The results were dramatic: carnosine almost totally reversed both the opacity and the light scattering in the AGE samples, bringing them back down to baseline levels. This demonstrated that carnosine had broken up the AGEs and restored the alpha-crystallin to its natural state, at least as far as optical properties were concerned. Treating pure, nonaggregated alpha-crystallin with carnosine was not expected to have any effect, and it didn’t.
The authors freely admitted that their laboratory experiments did not reflect the biochemical complexity of actual cataract formation, making it impossible to know the extent to which carnosine would have these effects in a living lens. They also noted, however, that the Russian clinical trials did show evidence of a reversal of lens opacity associated with cataracts—and that, ultimately, is what counts.
They also mentioned a variety of other effects attributed to carnosine from laboratory studies, but clinical benefits have not been demonstrated. One such effect is particularly intriguing because it may be another example of carnosine’s disaggregating action on protein complexes. The protein in this case is amyloid-beta, which is the primary constituent of senile plaque in the brains of Alzheimer’s victims.
Steroids Can Be Harmful as Well as Sugars
Crystallins are not the only kinds of proteins in lens cells, of course. There are many others, including esterases, a large class of enzymes that play important roles in many biochemical processes. Like the crystallins, the esterases can suffer glycation and cross-linking caused by sugars of various kinds. These harmful, age-related processes can also be caused by glucocorticoids, which are steroid hormones, such as cortisone, that play a major role in carbohydrate metabolism; they’re used clinically as anti-inflammatory agents in the treatment of diseases such as rheumatoid arthritis and asthma.
As valuable as they are for therapeutic purposes, glucocorticoids can be dangerous, especially in long-term use, because of their serious unwanted side effects, including cataracts, for which they’re a major risk factor. Although the mechanism by which glucocorticoids cause cataracts is unknown, there is suggestive evidence in the fact that these compounds can, like various sugars, inactivate esterases and cause their cross-linking to form large aggregates. It is believed that this process may play a major role in aging and in the complications of diabetes, and it may also play a role in Alzheimer’s disease, especially as regards the formation of amyloid-beta plaques.
More Evidence of Carnosine’s Benefits
A team of researchers at the University of Oxford recently investigated the beneficial effects of carnosine on the inactivation and cross-linking of esterases by several sugars and by a steroid called prednisolone-21-hemisuccinate (P-21-H); the latter is a metabolite of the potent synthetic glucocorticoid prednisolone, an anti-inflammatory, immunosuppressive, and antiallergic drug.2 The experiments entailed the incubation of an esterase from pig liver with various sugars and with P-21-H, in all cases both with and without carnosine. The results showed that the sugars and the steroid induced substantial inactivation and cross-linking of the esterase, and that carnosine provided strong protection from these degradative processes. They concluded,
It is increasingly apparent that carnosine not only has crucial anti-glycation and anti-oxidation roles, but that carnosinederived products have potential effects on a wide range of processes within the cell. Cross-linking or fragmentation of protein is associated with a large number of cellular malfunctions that give rise to disease. This present investigation clearly indicates that carnosine protected against the glycation and a steroid-induced inactivation of esterase and suppressed the extent of the cross-linking.
It’s Good Sense to Protect Your Senses
You may not be able to avoid aging, but you can go a long way toward staving off many age-related diseases, including cataracts. One of the best ways is to avoid diabetes, which, for most people (i.e., those who do not have a genetic predisposition to it), is probably the most easily preventable of the major chronic degenerative diseases of aging. And, as always, the judicious use of nutritional supplements can help prevent many of the ills that plague us, including some that threaten the most precious of our five senses: vision.
1. Seidler NW, Yeargans GS, Morgan TG. Carnosine disaggregates glycated a-crystallin: an in vitro study. Arch Biochem Biophys 2004;427:110-5.
2. Yan H, Harding JJ. Carnosine protects against the inactivation of esterase induced by glycation and a steroid. Biochim Biophys Acta 2005;1741:120-6.
Dr. Hyla Cass is a nationally recognized expert in integrative medicine, an assistant clinical professor of psychiatry at the UCLA School of Medicine, and the author or coauthor of several popular books, including Natural Highs: Supplements, Nutrition, and Mind-Body Techniques to Help You Feel Good All the Time and 8 Weeks to Vibrant Health: A Woman’s Take-Charge Program to Correct Imbalances, Reclaim Energy, and Restore Well-Being.