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LE Magazine February 2001

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The Role of Inflammation in Chronic Diseases


ACAM
Medical Conference Report
October 2000
Salt Lake City

by Ivy Greenwell

Other conference highlights:
Men with low insulin live the longest
Updates on testosterone and growth hormone replacement therapy
Nutritional approaches in the treatment of HIV
American College for Advancement
of Medicine (ACAM) is a non-profit organization dedicated to supporting research and education in alternative and complementary medicine. ACAM was founded in 1973, with a mission to make physicians and other health professionals aware of scientific advances relevant to holistic approaches to health and disease. Speakers at twice-yearly ACAM conventions are recognized experts in their fields. Each convention is an opportunity to gain more understanding about the underlying causes of many chronic disorders and learn about cutting-edge treatments. The October 2000 ACAM conference emphasized the role of chronic inflammation as a causative factor in the development and progression of a host of degenerative diseases.

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Introduction

Several years ago I heard a holistic practitioner say, “If we prevent inflammation, we can prevent Alzheimer's disease.” I was stunned. The mainstream view was, “If you live long enough, you will develop Alzheimer's.” The same went for cataracts and cardiovascular disease. Then last June Paul Ridker, MD, a Harvard cardiologist, publicly stated, “We have to think of heart disease as an inflammatory disease, just as we think of rheumatoid arthritis as an inflammatory disease.” He asserted that it's inflammation that leads to pieces of arterial plaque breaking off and causing heart attacks, even in people with normal or low cholesterol. Recently headlines announced that men regularly taking non-steroidal anti-inflammatories (NSAIDs) such as ibuprofen lowered their risk of prostate cancer by 66%; some risk reduction with NSAID use has also been reported for breast cancer and colon cancer. On a minor but important note, Dr. Nicholas Perricone, an innovative dermatologist, is now saying (or at least implying) that if we prevent inflammation, we can prevent a lot of skin aging.

Because of our new awareness of the importance of inflammation, it is not surprising that the most recent conference of the Academy for the Advancement of Medicine (ACAM) had inflammation and infection as its main theme. Only by understanding the mechanisms involved in the pathogenesis of diseases such as AIDS, cancer or Alzheimer's disease can we develop effective therapies. The growing understanding of the major role that oxidative stress and inflammation play in the development and progression of various pathologies has brought progress in devising more effective treatment protocols. In addition, the conference also included lectures and workshops dealing with updates in hormone replacement. Here are some of the highlights.

“The brain on fire”—Inflammation as the key to neurodegenerative diseases

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The brain in a state of chronic inflammation is, in Perlmutter's colorful phrase, "the brain on fire." Current therapies "treat the smoke, but not the fire."

David Perlmutter, a neurologist and director of the Perlmutter Health Center in Naples, Florida, and the author of BrainRecovery.com — Powerful Therapy for Challenging Brain Disorders, delivered an exciting lecture on the nature, prevention and treatment of neurodegenerative diseases such as Alzheimer's and Parkinson's. He concentrated on two factors: inflammation and glutathione depletion. Once we understand the critical importance of inflammation and glutathione depletion in brain diseases, we can take steps to prevent or even reverse the damage.

First, Dr. Perlmutter presented evidence that the current mainstream drugs such as Aricept are “essentially useless” in actually treating Alzheimer's disease. Their effectiveness is minimal at best, while their side effects include vomiting, dizziness and insomnia. These drugs do not correct the underlying inflammation. The brain in a state of chronic inflammation is, in Perlmutter's colorful phrase, “the brain on fire.” Current therapies “treat the smoke, but not the fire.”

The first real breakthrough in the understanding and treatment of Alzheimer's disease has been the discovery that the use of aspirin and NSAIDs such as ibuprofen (Advil) has a very significant protective effect. In one large study of those who used aspirin, NSAIDs or acetaminophen, NSAIDs reduced the risk of Alzheimer's disease to only 40% that of nonusers. Aspirin reduced the risk to 74%. Acetaminophen, however, raised the risk by 35% (this may have something to do with a toxic metabolite of acetaminophen, which depletes glutathione).

This finding is of tremendous importance to arthritis sufferers—they must become aware that their choice of a pain reliever is crucial in determining their risk of developing Alzheimer's disease. The effectiveness of ibuprofen is likely to stem from its superior ability to inhibit Nuclear Factor kappa B (NFkB), a transcription factor that switches on the production of inflammatory cytokines that initiate the process of cell death. It also supports Dr. Perlmutter's thesis that inflammation (“fire”) is at the core of Alzheimer's disease, and may turn out to be far more important than the beta-amyloid plaque.

We need to put out the fire in the brain—that is, reduce inflammation. Fortunately, we have some knowledge about how to accomplish this goal. For instance, we know that simply by taking nonsteroidal anti-inflammatories on a preventive basis, we can cut the risk of developing the disease by as much as 60%.

Can anti-inflammatories be used not only for prevention of neurodegenerative diseases, but also as treatment? Indomethacin, a well-known nonsteroidal anti-inflammatory, has been found to produce improvement in Alzheimer's patients, Perlmutter pointed out. The improvement was modest, but dramatic in the light of the fact that over the six-month course of the study the placebo group continued to deteriorate. Currently there is also great interest in the effect of selective COX-2 inhibitors (Celebrex, Vioxx) on the prevention of Alzheimer's disease, Perlmutter said. A few participants were concerned that “we may discover the price later on,” but for now we simply have to wait for more research findings. The main point is there has been a revolution in medical thinking. The gloomy dogma that nothing can be done to prevent Alzheimer's is giving way to an increasing awareness that reducing inflammation is powerful prevention. And now that we have those expensive COX-2 inhibitors, with more underway, the drug companies are certainly interested.

Pharmacological NSAIDs are not the only way to reduce inflammation. Fish oil has been shown to be an effective natural anti-inflammatory. The consumption of fish oil results in a different composition of cell membranes, with less arachidonic fatty acid available for the production of pro-inflammatory cytokines. Animal studies showed that diets containing fish oil profoundly reduce the levels of pro-inflammatory chemicals such as tumor necrosis factor alpha (TNF alpha) and various interleukins. Flax oil, a rich source of short-chain omega-3 fatty acids, also appears to be anti-inflammatory, though to a lesser degree. Epidemiological studies have amply demonstrated that frequent fish-eaters enjoy much better health, including less cognitive impairment and lower incidence of Alzheimer's disease, than those who eat little or no fish.

In addition, all antioxidants are also anti-inflammatory. Alpha lipoic acid and various flavonoids (such as those found in green tea and blueberries) may be particularly effective. A diet that emphasizes fish and seafood rather than meat, along with antioxidant-rich fruits and vegetables, can be useful in preventing degenerative brain disorders. This type of anti-inflammatory diet can make all the more difference with the right supplementation.

Perlmutter, however, placed special emphasis not on reducing inflammation once it has already started, but on trying to prevent it in the first place. “It's best to prevent inflammation from starting, rather than use drugs to dampen it,” he said. He emphasized that inflammation in the brain is particularly difficult to control. Cerebral inflammation tends to be self-perpetuating. We know that head injury and strokes (including mini-strokes), as well as various toxins and infections, produce inflammation and increase the risk of neurodegenerative disease. But few people know about the role of excess blood sugar in producing inflammation and thus contributing to the death of neurons. Perlmutter observed that Ronald Reagan's notorious sweet tooth might have contributed to the pathogenesis of his Alzheimer's disease.

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A diet that emphasizes fish and seafood rather than meat, along with antioxidant-rich fruits and vegetables, can be useful in preventing degenerative brain disorders.

Perlmutter cited a Dutch study that found a more than quadruple risk of dementia in type II diabetics who use insulin. On the other hand, calorie restriction, which profoundly reduces blood sugar and insulin, is perhaps the best dietary protection against age-related brain damage. Consuming fewer calories translates into lesser production of free radicals. In addition, glucose can damage proteins, modifying them to pro-inflammatory compounds called AGEs (Advanced Glycosylation End Products). AGE -modulated beta-amyloid is extremely pro-inflammatory. One way or another, Perlmutter kept returning to the theme of reducing inflammation as a means of preventing, and possibly even treating, Alzheimer's disease.

Apart from anti-inflammatory supplements, magnesium may also prove a useful neuroprotector. One cause of neuron death is excess influx of calcium ions. If magnesium is present in sufficient concentration, the resulting “magnesium block” (magnesium is a natural calcium channel blocker) can save the neurons.

People who have suffered head trauma, small strokes or infections affecting the brain are especially likely to have the kind of low-grade cerebral inflammation that makes them more susceptible to developing Alzheimer's disease. These high-risk individuals should be made aware that they can reduce their risk with fish oil, NSAIDs, lipoic acid, flavonoids and through calorie restriction.

Those protective measures should be practiced by all of us. The dismal prediction is that by the year 2030 there will be nine million Alzheimer's victims in the United States. Some even predict that the economic burden of Alzheimer's disease alone will be enough to bankrupt the medical system. Such disaster can be averted through relatively simple means. It is time to educate the public about the prevention of brain diseases.

Parkinson's disease and “The glutathione miracle”


Perlmutter went on to discuss his approach to Parkinson's disease. It is more than a brain disease, he said. Parkinson's is a systemic disease as well, with the whole body involved. More specifically, Parkinson's patients tend to be poor detoxifiers. They show low levels of glutathione not only in the brain (especially in the dopamine-producing region of substantia nigra), but also in the liver. This may be why exposure to pesticides and herbicides can be so damaging to individuals with a genetic vulnerability to Parkinson's. We all have to deal with a tremendous toxic burden, but those who happen to be poor detoxifiers are at a special risk.

The central feature of Parkinson's is the progressive destruction of substantia nigra, resulting in a profound deficiency of the neurotransmitter dopamine. Mainstream treatment centers on the use of l-dopa, a precursor of dopamine. This approach to increasing dopamine works for a limited time, though not without severe side effects, including further brain damage. “The very drug that's used to treat the smoke increases the fire,” Perlmutter stated. It turns out that l-dopa reduces detoxification. L-dopa also increases the conversion of S-adenosyl-methionine (SAMe) to homocysteine, and thus promotes vascular disease. At the same time, it's sometimes not possible to take patients with advanced Parkinson's off l-dopa. It may be possible, however, to counteract the drug's side effects and increase the patient's motor ability through a relatively simple alternative treatment.

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Within less than an hour of the injection, Parkinson's patients experienced an almost complete restoration of the ability to walk, turn around and move their arms.

Perlmutter's holistic approach is based chiefly on the need to increase detoxification, and thus enhance glutathione levels. The most dramatic part of Perlmutter's presentation consisted of slides showing a profound improvement in Parkinson's symptoms after intravenous glutathione. Within less than an hour of the injection, Parkinson's patients experienced an almost complete restoration of the ability to walk, turn around and move their arms. Perlmutter calls this “the glutathione miracle.” He uses 1200 mg of injectable glutathione at first, then lowers the dose to 600 mg per injection. The injections are given two days apart. The effectiveness of the treatment has been validated in a controlled study. Many holistic physicians already use intravenous glutathione as part of their treatment for Parkinson's disease.

If the treatment is discontinued, its benefits last for up to four months after the end of the treatment. Besides acting as a detoxifier and lowering oxidative stress, glutathione may also enhance the sensitivity of dopamine receptors in Parkinson's patients, Perlmutter speculated. He also mentioned that intravenous glutathione is immediately effective against irritable bowel syndrome and diarrhea.

Is there a more convenient way to increase glutathione levels, for longevity in general and as part of a preventive neuroprotective protocol? It turns out that lipoic acid is the most effective supplement for raising glutathione—especially if it is taken together with N-acetyl-cysteine (NAC) and vitamins C and E. In addition, the amino acid glutamine is, like NAC, an important precursor of glutathione. Silymarin (milk thistle extract) has also been shown to increase glutathione in the liver.

In addition, lipoic acid is known to chelate iron. The elevated levels of free iron in Parkinson's patients increase free-radical damage and the destruction of neurons. And, like ibuprofen, lipoic acid inhibits NFkB and thus the production of inflammatory cytokines.

Perlmutter mentioned other helpful supplements, including CoQ10, which enhances mitochondrial function and is known to be low in the cerebral mitochondria of Parkinson's patients (and, interestingly, also of their spouses). Ginkgo biloba was also discussed. Ginkgo has been shown to have many neuroprotective properties, including the protection of brain mitochondrial glutathione against oxidation. Ginkgo also inhibits the enzyme monoamine oxidase B (MAO-B), and thus helps protect dopamine against quick degradation. The drug seleginine (Deprenyl) also acts as a MAO-B inhibitor.

Predictably, there also arose some controversy over coffee, recently shown to be protective against the development of Parkinson's disease. Raising cyclic adenosine monophosphate (cyclic AMP—a “second messenger” that amplifies the hormonal message) has been shown to protect against Parkinson's.

“Caffeine dramatically increases cyclic AMP and decreases the risk of Parkinson's,” Perlmutter said. Caffeine also competes for receptors with adenosine, an inhibitory compound. By displacing adenosine, caffeine indirectly increases the action of dopamine.

Perlmutter condemned the use of long-term antibiotics. Certain antibiotics are mitochondrial inhibitors. “If you increase antioxidants, you don't need long-term antibiotics,” he stated. He also suggested that if a patient is put on statins, s/he ought to take supplemental CoQ10 to try to compensate for the CoQ10 deficiency induced by the drug. (Incidentally, a recent British study has found that statins appear to reduce the risk of dementia. As in the case of heart disease and stroke, this may be due to the anti-inflammatory properties of statins.)

One conference participant, an MD from England, suggested that supplementing with Vitamin B12 can be of enormous importance in treating dementia. He described a patient of his whose dementia virtually disappeared after treatment with B12. Many elderly are deficient in this vitamin, crucial for brain function. B12 also increases the oxygen-carrying capacity of red blood cells, and helps lower homocysteine. Dr. Perlmutter agreed that B12 should be an important part of the treatment. He also discussed magnesium as protective against excess calcium ion influx.

In summary, current research findings suggest the following: take lipoic acid and other antioxidants, eat fish and/or take fish oil, drink coffee (unless you can't tolerate it) and be happy. And forget about dessert. Calorie restriction still appears to be the most potent brain saver.

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