Fight AGE with Cinnamon
Can Cinnamon Compounds
Help Prevent AGE?
Their antidiabetic action may be due in part to their
suppression of carbonyl stress, an important factor in aging
By Will Block
uppose you were diabetic (but let’s hope you’re not). Chances are good that apple pie would not be on your doctor’s list of recommended foods. Apple pie is, after all, somewhat of a “carbohydrate bomb,” with all that flour and sugar—and, of course, apples, which are themselves 13% carbohydrate by weight. Diabetics must be especially careful to regulate their intake of carbs, and all of us should try to avoid “spikes” in our blood sugar (glucose) levels from eating high-glycemic-index foods, especially if we eat more than small amounts of them. The more such foods we eat at a given meal, the greater the overall glycemic load on our system.
But could apple pie be all that bad for you? We’re talking about apple pie, as in “Mom and . . .” Being against it sounds positively un-American! What would your Mom think? Well, she might concede that apple pie may not be the ideal food for diabetics, but if she happened to be a particularly savvy nutritional biochemist, she would also be quick to point out that the best apple pie (hers, of course) contains an ingredient that helps fight diabetes by enhancing the body’s insulin function, thereby helping to maintain healthy glucose metabolism—and more, as we will see below.
Cinnamon Flavonoids—The Best Part of Apple Pie
The “magic” ingredient that does this is cinnamon (Cinnamomum cassia). To be more precise, it’s certain compounds contained in the water-soluble portion of cinnamon bark. These compounds are obtained by subjecting cinnamon-bark powder to an aqueous extraction process, which leaves the undissolved, fat-soluble compounds as solids that can be filtered out. The water-soluble fraction of cinnamon contains numerous flavonoids with demonstrated biological activity against various diseases, including diabetes. (For a primer on flavonoids, see the sidebar.)
Of Flavonoids and Polyphenols
Other than green, the bright colors found in fruits, vegetables, berries, herbs, and flowers come mainly from flavonoids (aka bioflavonoids—same thing), of which there are six major classes. These classes are based on certain characteristic features of the molecular structures in question, but all flavonoids have one thing in common: they are all polyphenols. You have surely heard that term many times—probably always in a favorable context, because these compounds are renowned for their beneficial effects on our health.
But do you know what a polyphenol really is? It’s a simple concept, actually. It starts with phenol (FEE·nole), a small organic compound consisting of a benzene ring (a hexagon made of six carbon atoms, each with one hydrogen atom attached) in which one of the hydrogens has been replaced by a hydroxyl group, –OH.* If a larger molecule contains a phenol unit as part of its own structure, it’s called a phenolic compound. And if it contains more than one phenol unit, it’s called a polyphenolic compound, or simply a polyphenol. In many polyphenols, an additional hydroxyl group or two is attached to one or more of the benzene rings.
There are many different classes of polyphenols, of which the three major ones are tannins, lignins, and flavonoids. And the six major classes of flavonoids, with their many subclasses, comprise over 4000 different compounds, at least 50 of which are present in plant-based foods and beverages, notably berries, tea, and red wine. Unless (or even if) you’re a chemistry junkie, it’s hard to keep all the names straight and remember which compounds belong to which class.
Two notable features of dietary flavonoids (and of most biologically active polyphenols of other types) are: (1) they are beneficial to our health, and (2) they have virtually no known toxicity or adverse side effects.
The health benefits of polyphenol-rich foods have been recognized for thousands of years. Modern scientists have long believed that these benefits derive mainly from the polyphenols’ strong antioxidant properties (in laboratory experiments), but recent research has suggested that other mechanisms may be much more important in living organisms. In any case, polyphenols offer a host of documented benefits against heart disease, cancer, inflammation, dementia, vision disorders, allergies, impotence, viral infections, and more.
The flavonoids that appear to be primarily responsible for cinnamon’s antidiabetic action are called procyanidins (type A). These compounds are oligomers, a term used to denote polymers consisting of just a few molecular units, rather than many, as in most polymeric compounds. The individual units consist of the compound epicatechin (shown in the sidebar), the molecular structure of which allows the molecules to bind to each other in different ways, one of which is denoted type A.
Warning: Big Words Ahead
Epicatechin belongs to a family of compounds called catechins, various members of which are found in tea, chocolate, apples, berries, and grapes. One of them, epigallocatechin gallate (EGCG), is found mainly in green tea and is renowned for its many health benefits. In addition to forming procyanidins, catechins can combine to form other oligomers and various polymers, most of which are members of a class of compounds called proanthocyanidins (of which procyanidins are a subclass).
Proanthocyanidins are found abundantly in chocolate, apples, berries, red grapes, and red wine. (Red wine, of course, makes us think of the amazing, lifespan-extending compound resveratrol, which is not, however, a proanthocyanidin. In fact, it’s not a flavonoid of any kind—it’s a polyphenol of a different type.) Some proanthocyanidins are also found in cinnamon, which helps explain the health benefits of that delightful spice.
AGEs Are Bad—Especially in Diabetes
Recently, a team of researchers from the People’s Republic of China and Taiwan, with a colleague at Rutgers University in New Jersey, investigated the potential benefits of an aqueous cinnamon extract in alleviating an aspect of diabetes that causes much damage to various organs and tissues of the body. Among the compounds they identified in the extract they used were catechin, epicatechin, procyanidin B2, and various proanthocyanidin oligomers and polymers.
Their aim was to inhibit the formation of advanced glycation endproducts, or AGEs, which degrade normal cell structure and function. These deleterious substances are cross-linked protein complexes resulting from the chemical reaction of sugars—especially glucose (blood sugar)—with proteins in many organs and tissues of the body.
AGEs accumulate gradually, over a lifetime, in all of us, but this process is accelerated in diabetics, owing to chronically high blood glucose levels. AGEs are implicated in other chronic degenerative diseases of aging as well, and with the aging process itself. (For more on this subject, see
“How and Why to Prevent AGE Damage” in the March 2008 issue.)
Currently the most promising avenue of attack on the problem of AGEs seems to be the use of agents that reduce carbonyl stress, which is the damage done to our system by some (but by no means all) molecules containing the carbonyl group,
This atomic grouping is quite reactive, often in undesirable ways. One of them entails the initiation of a series of reactions called the Maillard process, which leads to AGEs: the carbonyl group in a sugar, such as glucose, reacts with the amino group (–NH2) in one of the amino acids in a protein. This reaction, called glycation, is the first step in the Maillard process, which was discussed in the Life Enhancement article mentioned above.*
How to Trap a Reactive Carbonyl Species
Carbonyl stress can be thought of as analogous to oxidative stress, which is the damage done to our system by reactive oxygen species (ROS). Our primary defense against ROS (including free radicals) is antioxidants, which scavenge and neutralize them. Similarly, carbonyl stress is the damage done to our system by reactive carbonyl species (RCS), and our primary defense here is agents that scavenge and neutralize them, thereby preventing the damage they can cause when they participate in unwanted reactions, such as the glycation of proteins.* These helpful compounds are usually called reactive carbonyl trapping agents (the punchier term “anticarbonyls” is not used); they could also be called anti-AGE agents.
The best known anti-AGE agent is the experimental drug aminoguanidine (a chemical relative of the rocket fuel hydrazine), which is quite effective in inhibiting the Maillard process. Unfortunately, though, aminoguanidine has undesirable side effects in patients with diabetes (no, it does not make them explode), so it has not been approved for clinical use. Hence the search is still on for something that is both effective and safe—which brings us back to the aqueous cinnamon extract studied by the Chinese researchers.
Cinnamon Strongly Inhibits AGE Formation
For their experiments, the researchers used solutions of glucose and bovine serum albumin (a protein from cow’s blood), incubated at body temperature for 7 days in order to induce the Maillard process and rapid AGE formation. To these solutions they added aqueous cinnamon extracts or various components of the extracts to determine which ones would most effectively inhibit AGE formation.
The results showed strong AGE inhibition by catechin, epicatechin, and procyanidin B2 (a type B procyanidin—there was no mention of type A procyanidins). The inhibition percentages were about 55%, 57%, and 70%, respectively, vs. 80% for aminoguanidine, which was used as a reference standard.
Then the researchers tested these same three compounds against methylglyoxal, a reactive dicarbonyl compound (one that contains two carbonyl groups) that’s produced as an intermediate in AGE formation. Here the cinnamon compounds were even more effective than aminoguanidine: their percentage efficiencies in trapping methylglyoxal were all about 93%, vs. 72% for aminoguanidine. (For more on the significance of dicarbonyls, especially in diabetics, see the
article on p. 17 of this issue.)
The authors concluded,
In summary, cinnamon bark has been reported to benefit people with diabetes because of its antioxidant and insulin-enhancing activities. Our study found that cinnamon bark extract could inhibit the formation of AGEs, which have been implicated in the pathogenic process of diabetic complications. The inhibitory effect of cinnamon bark on AGE formation is mainly attributed to the antiglycation activities of some of its phenolic constituents, such as catechin, epicatechin, and procyanidin B2, likely trapping reactive carbonyl species. Apart from proanthocyanidin dimers, findings from the present study also supported the effectiveness of proanthocyanidin oligomers and polymers as natural antiglycation agents.
Treat Yourself to Some Cinnamon
The authors noted that the polyphenolic compounds that have been found in laboratory experiments to be effective anti-AGE agents are, for the most part, also effective antioxidants in laboratory experiments—but often not in living organisms. The two actions may be related, but most of the clinical trials of polyphenolic antioxidants in patients with diabetes—a disease in which both oxidative stress and carbonyl stress play large roles—have been disappointing.
On the other hand, the benefits of some such compounds are undeniably real, so whether they act as antioxidants or in some other manner is not all that important, except to scientists.* It’s gratifying, in any case, that cinnamon, which is known to mimic the effects of insulin and enhance glucose metabolism, also appears to have a potent anti-AGE effect. Not bad for a spice that used to be associated mainly with treats such as Mom’s apple pie.
- Peng X, Cheng KW, Ma J, Chen B, Ho CT, Lo C, Chen F, Wang M. Cinnamon bark proanthocyanidins as reactive carbonyl scavengers to prevent the formation of advanced glycation endproducts. J Agric Food Chem 2008;56:1907-11.
Will Block is the publisher and editorial director of Life Enhancement magazine.