for the Brain? Could Mastic Help
It kills Helicobacter pylori, which may indirectly
contribute to the disease’s development
By Will Block
emember Rube Goldberg? He was famous for his cartoon drawings of comically, crazily complicated contraptions in which an action initiated at one end became a desired result—the performance of some simple task, such as feeding the dog or killing a bug—at the other end. It all occurred via a convoluted series of wildly improbable—but more or less possible—mechanical, chemical, and even animal linkages. Following the tortured path from the initial cause to the final effect was great fun, thanks to Goldberg’s outlandish imagination and clever use of engineering principles (he was an engineer by training, by the way).
Although we don’t usually think of the human body as a Rube Goldberg contraption, an analogy can be made in the sense that some biological effects appear to be very remote from their supposed causes, and the biomechanical or biochemical linkages between them can be complex and surprising.
One of the many challenges in medical research (and scientific research in general) is to deduce the true relationships between apparent causes and effects in a given system: is there really causation—the inexorable progression from cause to effect following the laws of physics and chemistry—or is there merely a correlation masquerading as cause and effect? The distinction is critical, and failing to make it correctly (or even at all) can lead to all manner of erroneous conclusions.* Sometimes the connections in a chain of events are clear and relatively easy to nail down; other times they can be maddeningly elusive—if they exist at all.
Put on Your Sherlock Holmes Hat
Let’s play medical detective and look at a series of events that seem to lead from a cause to an effect so far-fetched that one would need a Goldbergian imagination to dream something like this up. The question to keep in mind is: Is the chain of events causal all the way, or are there mere correlations involved that could fool us into thinking in terms of cause and effect?
© iStockphoto.com/Sean Locke
We begin with a topic that’s familiar to readers of this magazine, especially those who have reason to take the dietary supplement mastic, an aromatic gum resin known for its anticancer and anti-inflammatory effects and for its ability to kill a number of species of harmful microorganisms, most notably one that’s implicated in a variety of gastrointestinal ailments: Helicobacter pylori.
Helicobacter pylori Can Cause . . .
H. pylori is a nasty little bacterium that infects the gastrointestinal tracts of over half of the world’s adult population. It’s now known to be the primary cause of the vast majority of peptic ulcers (ulcers of the stomach or duodenum), and it’s strongly implicated in the development of stomach cancer. In those who carry the H. pylori bug, however, the most common affliction is gastritis.
. . . Gastritis, Which Can Reduce . . .
Gastritis is an inflammation of the stomach lining. It’s usually asymptomatic, but it can cause nausea, vomiting, and abdominal discomfort or pain, and it can lead to ulcers and even stomach cancer. In severe cases, it can also lead to anemia due to a slow loss of blood from the stomach. The disease can be caused by many factors, but the most common is H. pylori infection. A chronic version of the disease that afflicts primarily older people, especially those with H. pylori infection, is called atrophic gastritis, which entails atrophy of the gastric mucosa (the stomach’s inner lining). This leads to a reduction in the stomach’s production of a substance called intrinsic factor.
. . . Intrinsic Factor, Which Is Essential for the Absorption of . . .
Intrinsic factor is a protein secreted by cells of the gastric mucosa. This protein is essential for the body’s ability to absorb a certain nutrient from our food into the bloodstream. If the production of intrinsic factor is reduced owing to atrophic gastritis or any other cause, the result is a reduction in the body’s ability to absorb that vital nutrient: vitamin B12.
. . . Vitamin B12, Which, with Folic Acid, Helps Regulate . . .
Vitamin B12 (also known as cyanocobalamin) is essential for cell replication and plays a critical role in the cells’ production of the nucleic acids DNA and RNA. It supports growth, appetite, and the formation of red blood cells and myelin sheaths (the insulating sheaths on nerve fibers), and it appears to be important for proper immune function. Ingesting sufficient amounts of vitamin B12 is especially important as we grow older, as our ability to absorb it diminishes with the age-related decline in our production of intrinsic factor. Also in decline as we age is a substance whose functions are intimately tied to those of vitamin B12: the B-vitamin known as folic acid, or folate. Together, these vitamins serve to control our blood levels of homocysteine.
. . . Homocysteine, Elevated Levels of Which Can Damage the . . .
Homocysteine is a sulfur-containing amino acid that plays an important role in cellular metabolism, and it’s harmless as long as its levels remain within the normal range. If those levels rise, however (as is common with advancing age and vitamin B12 or folic acid deficiency), a Pandora’s box of horrendous consequences is opened, spewing harm of myriad kinds throughout the body.
Elevated levels of homocysteine are strongly linked to, among other things, an increased risk of vascular disease—cardiovascular disease in particular, but also peripheral vascular disease (including deep vein thrombosis) and cerebrovascular disease. This comes about primarily via homocysteine’s deleterious effects on the endothelium.
. . . Endothelium, Whose Damage Can Lead to . . .
Endothelium is the name given to the layer of thin, flat, smooth, cells that constitute the inner lining of our blood vessels. Far from being just a lining, the endothelium is physiologically active and plays a central role in regulating the contractions and dilations of our blood vessels, thereby regulating our blood pressure. If the endothelium’s integrity is compromised by excessive levels of homocysteine in the blood, its effectiveness diminishes, paving the way for hypertension (high blood pressure). To make matters worse, damage to the endothelium encourages the development of atherosclerosis.
. . . Atherosclerosis, Which Can Lead to . . .
Atherosclerosis entails the formation of plaque deposits, consisting primarily of cholesterol and other lipids, which take root in the damaged endothelium and grow ever larger. This is a setup not just for impaired blood flow due to partial occlusion of the blood vessel but also for the formation of a thrombus (an attached blood clot), which incorporates itself into the plaque. As long as it remains there, the thrombus does no harm other than by contributing to the occlusion.
If, however, the plaque ruptures and the thrombus breaks free, as sometimes occurs, the latter becomes an embolus (a detached blood clot), which can cause a total occlusion at some point downstream—in the brain, for instance. If that occurs, the result can be a stroke or, at least, a transient ischemic attack.
. . . Transient Ischemic Attacks, Which Can Lead to . . .
Transient ischemic attack (TIA), also called ministroke, is the result of a sudden but temporary shutoff of the blood supply to a given region of the brain. The resulting deprivation of oxygen, glucose, and other nutrients will damage and perhaps kill the neurons (nerve cells) in the affected region. And that, especially if it happens repeatedly, can lead to vascular dementia.
. . . Vascular Dementia, Which Is Closely Related to . . .
Vascular dementia, as the name implies, is dementia related to the brain’s vasculature, or blood vessels. It occurs mainly when a series of TIAs causes cumulative damage in certain areas of the brain. Despite its relatively simple “plumbing”-related origin, vascular dementia has ramifications that make it more complex than it seems. In particular, it is known to contribute to the clinical manifestations and the worsening of another type of dementia with which it shares numerous characteristics, namely, Alzheimer’s disease.
. . . Alzheimer’s Disease
Alzheimer’s disease is a neurodegenerative disease characterized by the progressive damage to, and eventual death of, tissue in certain regions of the brain. This is accompanied by a gradual loss of memory and other cognitive functions as well as by behavioral changes and the loss of ability to function in the ordinary activities of daily living. Little by little, the victim’s very personality is eroded away, and finally life itself is extinguished.
What Can We Deduce, Dr. Watson?
And to think that all this can come about because of a common bacterial stomach infection. But can it? Does it? In truth, we don’t know. All we have is the intriguing scenario described above and a variety of evidence suggesting that it might be true, at least to some degree. That evidence has been discussed in a series of papers published recently by a team of researchers from the Aristotle University of Thessaloniki in Greece.
Their interest was apparently prompted by an Italian study suggesting a possible link between H. pylori infection and Alzheimer’s disease. In that study, an H. pylori infection was inferred from the unusual prevalence, in the Alzheimer’s patients’ blood, of specific antibodies that develop in response to the bacterium. Such a test cannot distinguish, however, between current and old infections, because the antibodies can remain in one’s system for years after the infection itself has been eliminated.
Alzheimer’s Patients Had High Rate of
H. pylori Infection
The Greek researchers undertook a similar study using the “gold standard” test for H. pylori—histologic analysis of biopsied samples of the gastric mucosa—to be able to tell for sure whether or not an active infection was present. Significantly, they found that the incidence of H. pylori infection was much higher (88%) in a group of 50 Alzheimer’s patients than in a group of 30 age-matched controls (47%) who had anemia but not Alzheimer’s. They also found that the levels of an anti-H. pylori antibody were twice as prevalent (34% vs. 17%) in the Alzheimer’s patients as in the controls.
In addition, they found that the Alzheimer’s patients’ homocysteine levels were significantly higher (by 31%) than those of the controls, which agrees with the findings of other studies. Finally, they found that the incidence of chronic atrophic gastritis affecting both the main body of the stomach and the antrum (the lower part, near the pyloric sphincter) was 98% in the Alzheimer’s patients vs. 70% in the controls.
These findings are consistent with those of other studies indicating that both H. pylori–induced gastritis and elevated homocysteine levels are associated with increased risks for atherosclerosis and for cardiovascular and cerebrovascular disease. Homocysteine is also an independent risk factor for dementia of both the vascular and Alzheimer types.
What’s the Mechanism? Is There a Mechanism?
But does all this suggestive evidence demonstrate causation between H. pylori and Alzheimer’s disease? No—to do that would require researchers to show that eradicating H. pylori in Alzheimer’s patients altered the course of their disease, or that eradicating it in nondemented individuals reduced the risk for dementia. Such studies would necessarily be of long duration and would be very costly.
Even if a causal link could be established, it would still not prove that the mechanism outlined above was valid—that would require a lot more research. It’s worth noting that the Greek authors posited no less than six other possible mechanisms by which H. pylori infection might contribute to the development of Alzheimer’s disease; it’s conceivable that all seven mechanisms could contribute to some degree, or that none of them do. The subject is much more complex than our oversimplified discussion implies.
H. pylori—Out of Africa
"Can we all get along?" was the plaintive query by the violent thug Rodney King in the inflammatory aftermath of his beating and arrest in Los Angeles in 1991. As a society, we often don’t get along very well, alas. As a species, however, we have been getting along—unknowingly until very recently—with a microbial thug that has brought more pain and suffering to mankind than the likes of King could ever imagine. And now that we know what we’re dealing with, we don’t want to get along with it any more—we want to get rid of it.
We’re speaking, of course, of Helicobacter pylori, the source of almost all gastritis and peptic ulcers throughout recorded history, and for a long time before that. For how long has Homo sapiens been harboring this beastie in its collective belly? For at least 58,000 years. That’s the remarkable conclusion drawn by an interdisciplinary team of scientists from Germany, England, France, South Africa, the United States, Spain, and Sweden.
© iStockphoto.com/Jan Rysavy
Using analytical techniques from population genetics and molecular biology, the researchers studied the DNA patterns of variant bacterial strains of H. pylori from 51 different ethnic sources around the world, to test whether their patterns of geographic distribution mimic those of human beings. They do, suggesting strongly that humans and H. pylori coevolved in the same place—East Africa, the probable cradle of anatomically modern humans—and that early humans took H. pylori with them as they migrated across the face of the Earth.
The authors concluded,
In this paper we have shown that the key patterns in the distribution of H. pylori genetic diversity mirror those of its human host. . . . Finally, simulations predict that H. pylori has spread from East Africa over the same time scale as anatomically modern humans. These extraordinary parallel population genetic patterns between H. pylori and its human host all demonstrate an old association predating the “out of Africa” event. The results further point to a scenario
where H. pylori and human populations have been evolving intimately ever since, with limited long-range transmission by horizontal infections.
- Linz B, Balloux F, Moodley Y, Manica A, Liu H, Roumagnac P, Falush D, Stamer C, Prugnolle F, van der Merwe SW, Yamaoka Y, Graham DY, Perez-Trallero E, Wadstrom T, Suerbaum S, Achtman M. An African origin for the intimate association between humans and Helicobacter pylori. Nature 2007;445(7130):915-8.
MCI Patients Also Had High Rate of
H. pylori Infection
In a subsequent study of a similar nature, the Greek team investigated the relationship between H. pylori infection and mild cognitive impairment (MCI), the precursor condition to Alzheimer’s disease. The results were very similar to those of the first study, providing yet more support to the premise that H. pylori is a risk factor for the development of cognitive impairment and dementia. It’s not a major factor, however, because the number of Alzheimer’s victims worldwide (about 26 million) is minuscule compared with the number of H. pylori victims (about 3.3 billion, or about 130 times as many).
This illustrates an important principle. Even if causation is established in any given situation, we must still ask another key question: What is the probability? In other words, if a given effect can occur, how likely is it that it will occur? Some probabilities are high; others are so low as to be negligible. It takes great expertise to be able to evaluate such matters competently.
So we’re left with the intriguing premise that H. pylori may be a contributing factor—probably one of many—in the development of MCI and Alzheimer’s disease. If that’s true, it provides yet another reason for wanting to rid ourselves of this awful bacterium, whose ability to cause gastrointestinal grief has apparent side effects that few people could have imagined.
Fortunately for us, it doesn’t take a Rube Goldberg-type contraption to kill the bug. All we need is mastic.
- Kountouras J, Tsolaki M, Gavalas E, Boziki M, Zavos C, Karatzoglou P, Chatzopoulos D, Venizelos I. Relationship between Helicobacter pylori infection and Alzheimer disease. Neurology 2006;66:938-40.
- Kountouras J, Gavalas E, Zavos C, Stergiopoulos C, Chatzopoulos D, Kapetanakis N, Gisakis D. Alzheimer’s disease and Helicobacter pylori infection: defective immune regulation and apoptosis as proposed common links. Med Hypoth 2007;68:378-88.
- Kountouras J, Tsolaki M, Boziki M, Gavalas E, Zavos C, Stergiopoulos C, Kapetanakis N, Chatzopoulos D, Venizelos I. Association between Helicobacter pylori infection and mild cognitive impairment. Eur J Neurol 2007;14:976-82.
- Kountouras J, Gavalas E, Boziki M, Zavos C. Helicobacter pylori may be involved in cognitive impairment and dementia development through induction of atrophic gastritis, vitamin B-12-folate deficiency, and hyperhomocysteinemia sequence. (Letter) Am J Clin Nutr 2007;86:805-6.
- Malaguarnera M, Bella R, Alagona G, Ferri R, Carnemolla A, Pennisi G. Helicobacter pylori and Alzheimer’s disease: a possible link. Eur J Int Med 2004;15:381-6.
Will Block is the publisher and editorial director of Life Enhancement magazine.