With H. pylori, Action Begins in the Mouth
When a beaver dams a stream to make a pond and build his lodge—an ambitious structure of branches, twigs, and mud—the job never seems to end. The beaver is busy, busy, every day, fetching more material to plug a hole here or reinforce a weakness there. If he didn’t, the whole structure would gradually disintegrate under the relentless erosive action of the stream, which is as good at gnawing away the dam as the beaver is at gnawing down trees for branches to use as building material (and as food). If all goes well for the beaver, there exists a state of dynamic equilibrium, in which these two opposing forces cancel each other out so as to maintain a stable structure—his nice dam home.
Inside our bodies, a similar drama is constantly unfolding at the cellular level. It too involves a structure consisting of “branches” and “twigs”: our skeleton. Bones don’t just grow to a certain size and then freeze, never to change for the rest of our lives. There is a dynamic equilibrium in our bones, as one force constantly builds bone material and the other constantly destroys it—ideally at exactly the same rate so that there is no net change.
Did You Know Your Bones Were Being Remodeled?
Our bone-building “beavers” are cells called osteoblasts, which create new bone material (mainly from the minerals calcium and phosphorus); their opposite numbers, the bone-destroying “streams,” are cells called osteoclasts, which remove old material, in a process called resorption. Between them, they maintain a process that scientists call remodeling. This is not like the highly visible remodeling we do in our homes when we upgrade the kitchen or add a room. In bone remodeling, nothing really changes: the size and shape of the bones remain constant, but their structural integrity is continuously renewed as old material that’s getting weak is replaced with strong, new material. It’s a great system.
But—the system gradually breaks down as we age. The balance point in the dynamic equilibrium between bone formation and bone resorption shifts slowly toward the latter, as formation slows down or resorption speeds up, or both. As the bone mineral density decreases, our bones gradually become porous and brittle. The initial stage of this process is called osteopenia (“poor bone”); if it becomes more severe, it’s called osteoporosis (“porous bone”). All adults are susceptible to this disease, but its most prevalent in postmenopausal women, owing largely to the effects of estrogen loss.
A Bug in the Mouth Will Sometimes Go South
OK, we’ve talked about beavers and bones, and we’ll return to the bones (a mystery subject for now) a little later. Now it’s time for bugs and bellies. The bug in question is a bad bug, Helicobacter pylori, which besieges our bellies in nasty ways. This bacterium is notorious for causing gastritis (inflammation of the stomach lining), peptic ulcers, and stomach cancer. It infects about half of the world’s population. The reason why those
Modern medicine deals with H. pylori infections with a three-drug regimen called triple therapy, which is usually successful in eliminating the bug from the stomach and intestines within a few weeks (in particularly tough cases, a fourth drug is used, for quadruple therapy). That’s great, except for one thing: the gastrointestinal (digestive) tract begins at the mouth, not the stomach, and H. pylori commonly infects the mouth as well as parts south.
Whether or not the bacteria do much damage in the mouth is an open question. Even if they didn’t, though, we would still not want to harbor them there, for one simple reason: things in the mouth can go south. That’s why the reinfection rate with H. pylori is relatively high in people who have eradicated the bug in their stomachs and intestines—sooner or later, some of the bacteria in their mouths may migrate down there and take up residence all over again.*
*Another common risk is cross-infection in families, owing to intimate contact, such as kissing. See “Children’s H. pylori Infection Can Endanger the Family and “Parents Can Infect Their Children with H. pylori” in the June and October 2002 issues, respectively.
An Ancient Chewing Gum Kills H. pylori . . .
The gum-resin "tears"
of the mastic tree.
. . . And So Does an Ancient Candy
Another traditional therapy used for thousands of years (and over a wider geographic area, including Asia) is licorice, which has long been prized not just for its sweetness and distinctive flavor but also for its soothing and healing effects on gastrointestinal ailments. Licorice comes from the root of an herb (Glycyrrhiza glabra) that contains a wealth of biologically active compounds; many have antiulcer activity that is probably related to their ability to kill H. pylori bacteria.
Unfortunately, two of licorice’s most active compounds, glycyrrhizic acid and glycyrrhetinic acid, have a tendency to promote edema and hypertension if consumed in excessive amounts. To avoid this problem, most commercial licorice extracts used for medicinal purposes (as well as for most licorice candies) have been deglycyrrhizinated (de·gliss·sir·RYE·zin·a·ted), a chemical process to remove the offending acids. The resulting product is called deglycyrrhizinated licorice, or DGL, and it’s entirely safe to use. It’s also effective, because of the biological potency of the remaining components. The efficacy of licorice for gastrointestinal ailments was discussed in last month’s issue ( “Why Your Stomach Will Love Turmeric and Licorice”).
What’s in Your Pockets?
Like beavers, H. pylori bacteria want a nice, snug home where they can be cozy and safe. In our mouths, the best place for that is the periodontal pockets around our teeth. Down there, below the gum line, where sticky, destructive dental plaque builds up if we’re not assiduous about oral hygiene, the bugs settle in with other nasty bacteria, such as their sugar-eating, acid-spewing, plaque-creating, tooth-rotting friend Streptococcus mutans. That’s the bug primarily responsible for dental caries and periodontitis. The latter is a chronic inflammation of the connective tissue that surrounds the tooth root and attaches it to its socket in the jawbone. (Aha! We’re getting back to bones—the mystery will soon be solved.)
Periodontitis is a very common disease (one that far too many people ignore) caused by bacteria-rich plaque in the periodontal pockets. It’s often accompanied by gingivitis(inflammation of the gingiva, or gum) and the gradual detachment of the gums from the teeth, which deepens the pockets and makes things progressively worse. The acids generated by the S. mutans bacteria slowly eat away at the bone that constitutes the tooth sockets. These sockets are called alveoli in medical jargon, and the bone is called alveolar bone.
So, connecting the dots, we have bugs that are bad for our bellies living on the plaque in our periodontal pockets, where they’re a part of the pernicious preconditions leading to periodontitis—which attacks and degrades alveolar bone. Thus we could say that, in a manner of speaking, H. pylori is “bad to the bone” (please don’t groan—it took a lot of work to set up that joke). In reality, there is no evidence of a direct association between H. pylori and bone loss, but bone loss is certainly worth combating in any case, just as H. pylori is.
Ipriflavone Is a Bone-Builder
Various drugs are helpful in inhibiting bone loss or rebuilding lost bone, and so is a nutritional supplement called ipriflavone. This is a synthetic derivative of a natural plant compound called genistein. Ipriflavone’s efficacy in treating osteoporosis is well established by the results of numerous animal studies and human clinical trials, and it’s currently used as a prescription drug for that purpose in Japan, Italy, Hungary, and some other countries.1 The typical dosage is 600 mg/day, often in conjunction with 1 g/day of calcium; this amount has been shown (usually in postmenopausal women) to be effective in increasing bone mineral density, reducing bone pain, and reducing the incidence of bone fractures. (For more on ipriflavone, see the sidebar.)
The three principal soy isoflavones are genistein, daidzein, and glycitein, of which genistein is the most studied. It’s used in folk medicine primarily as a diuretic, and also as a laxative and for rheumatism and gout. Its name comes from that of another source of this compound: a small Eurasian shrublike herb (Genista tinctoria) having clusters of yellow flowers that yield a dye. The common name for this plant is dyer’s greenweed or dyer’s broom.
In addition to being a versatile antioxidant, genistein may have anticarcinogenic effects against prostate cancer (via its estrogenic activity) and against breast cancer (via its antiestrogenic activity).1 It has been speculated that its estrogenic properties may also help protect against osteoporosis by preventing bone resorption and promoting bone mineralization.
Although antiosteoporotic effects are obviously desirable, estrogenic effects are often not, so a compound with the former but not the latter would be a desirable alternative to genistein. Such a compound was found in the form of a synthetic derivative of genistein called ipriflavone; the “ipri” part of the name comes from the isopropoxyl group
*Isoflavones are a special type of flavones, which are one of the many kinds of flavonoids. All flavonoids (which are also called bioflavonoids) are polyphenols, which tend to be strong antioxidants.
Although ipriflavone is sometimes classified as a phytoestrogen, it should not be, because it’s not a plant compound (although it does appear in trace amounts in some soy sauces), and it has no estrogenic activity. Also, unlike the true flavones and isoflavones, which are polyphenolic compounds, ipriflavone is not a polyphenol.
An Italian research group has recently studied the ability of ipriflavone to stimulate the regeneration of alveolar bone in small holes they had drilled in rats’ jaws.2 Some holes were left empty to heal spontaneously, while others were packed with powdered ipriflavone or with various bone-repair substances. When the rats were killed 40 days later, it was seen that ipriflavone had significantly accelerated bone healing compared with the other substances and the untreated controls. In discussing this, the authors cited numerous studies showing that ipriflavone protects bones both by stimulating new bone formation and by inhibiting bone resorption, thus tending to reverse the age-related shift in the dynamic equilibrium mentioned earlier.
Another group of Italian researchers has been developing ipriflavone-impregnated biodegradable films that dentists can insert into the periodontal pockets of patients in order to maximize the amount of ipriflavone in close proximity to the alveolar bone.3They point out that conventional drug formulations for the mouth, such as toothpaste and mouthwash, have very poor penetration into the periodontal pockets. Manually inserted films can overcome this problem and get the ipriflavone molecules where they need to be.
Oral H. pylori—Get Rid of It!
We know there is a strong association between poor oral hygiene status, including periodontitis, and infection with S. mutans (which mastic combats, by the way, thereby combating plaque formation and periodontitis). But is there an association between poor oral hygiene and H. pylori infection? That question has vexed researchers, who have found confusing and contradictory results.4
The most recent study, done in India, concluded that there was no significant association between the two factors in the 134 people examined, but there was a high prevalence of H. pylori in their dental plaque, regardless of whether or not they had gastric H. pylori infection.4 This suggests that, for most people who are currently free of gastric infection, the door is open to either first-time infection or reinfection. Trying to rid the mouth of H. pylori is, therefore, a good idea—and a good way to do that is with mastic and licorice.
Why Is Mother Nature Laughing?
Wouldn’t it be nice if our teeth were as strong as a beaver’s? Although trees are not in our diet, thankfully, some of our foods present a challenge, especially to those with weakened teeth or false teeth—things such as nuts, corn on the cob, and even apples. Not to mention chewing gum and candy, both of which can be hard on our teeth and (unless they’re sugar-free) can rot them to boot.
How ironic, then, that two of the best agents—mastic and licorice—for combating H. pylori, a bacterium that enjoys living in our dental plaque, are derived from … chewing gum and candy! Mother Nature may still be laughing at her little joke.