CAUSES AND NUTRITIONAL THERAPIES FOR NEURODEGENERATIVE DISEASES

The Theron G. Randolph Lecture at the 35th Annual Meeting of the American Academy of Environmental Medicine (AAEM) was presented by David Perlmutter, MD, who titled his lecture "Powerful Nutritional Therapies to Mitigate Neuroinflammatory Disorders." The late Dr. Randolph was a founding member of the NOHA Professional Advisory Board. The following article just touches on Dr. Perlmutter's overall model for these diseases and on the therapies that he covered.

Neurodegenerative diseases, such as Alzheimer's, Parkinson's, and ALS (amyotrophic lateral sclerosis or Lou Gehrig's disease), have been shown to have many seemingly disparate causative factors, including foreign toxins from the environment (xenobiotics), infectious agents, genetic predispositions, toxins formed by our own metabolism1, electromagnetic radiation exposure, sex hormones, and pharmaceutical drugs. Interestingly, Dr. Perlmutter presents an overall understanding of these injuries, which specifically involves the mitochondria.

Agents triggering the cascade leading to the death of neurons in genetically susceptible individuals include toxins from the microorganisms in the gut, toxic metals and pesticides, food and environmental antigens, stress responses, and chronic infection.

Mitochondria are tiny structures within our cells and enclosed by their own membranes. They are the principal sites of ATP (adenosine triphosphate: our body's principal molecule for energy) production and they contain their own DNA (deoxyribonucleic acid) and ribosomes, replicate independently, and make some of their own proteins. In addition to the neurodegenerative diseases, inadequate energy production by the mitochondria is involved in many other diseases, including even stroke like episodes. Often, the mitochrondrial DNA becomes abnormal. "Oxidative damage to mitochrondrial DNA has been estimated to be 10-fold higher than damage to nuclear DNA" (in other words, to the DNA for the division of our cells).

The cornerstone of this emerging model seems to focus on the critically important role of mitochrondrial energy metabolism and its relationship to the toxic effects of excitatory neurotransmitters. In this model excitatory neurotransmitters (predominantly glutamate2) stimulate specific neuronal receptors, which, when altered by deficient ATP production leads to a self-perpetuating cascade of events ultimately culminating in neuronal death.

Mitochrondrial dysfunction has many deleterious consequences. However, possibly the most important is a change in the electrical potential across the membranes of the neurons in our brains. With normal mitochrondrial ATP production the magnesium ion blocks a receptor for the excitatory neurotransmitter glutamate. However, with inadequate mitochrondrial energy production the control is gone and calcium floods into the cell. The influx of calcium is pivotal in the cascade of events that leads to the death of the neuron.2

Mitochondria are tiny structures within our cells and enclosed by their own membranes. . . . Inadequate energy production by the mitochondria is involved in many other diseases, including even stroke like episodes.

"It is interesting to note that in Parkinson's disease, Huntingon's chorea, and Alzheimer's disease, mitochrondrial dysfunction leading to excessive free-radical production and oxidative tissue damage seems to be confined to the brain, despite the fact that the underlying mitochrondrial abnormality is systemic. . . . This may be explained by the unique susceptibility of the brain to mitochrondrial dysfunction and resultant excessive free-radical production since the brain uses approximately twenty percent of the total O2 consumption (while representing only one-fiftieth of the body weight)."

"It has long been known that there is a significant relationship between previous xenobiotic exposure and the risk of various neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. . . . If indeed [as described above] mitochrondrial dysfunction plays an important role in the pathogenesis of neurodegenerative diseases and the various studies indicating increased risk with xenobiotic exposure are valid, what mechanism could relate these two concepts?"

Replying, Dr. Permutter points out: Research has shown that certain xenobiotics inhibit energy production in our mitochondria. The question remains: Why are some people able to detoxify all the toxins and others cannot. Dr. Sidney Baker presented NOHA with fascinating material on "Detoxification and Healing,"1 including material on the sulfur-containing amino acids, especially methionine, and the production of glutathione with its powerful detoxifying potential.

Since the glutamate cascade is crucial in the destruction of neurons, a first step needs to be to avoid the ingestion of free glutamic acid (MSG), which is overwhelmingly prevalent in processed foods.

Dr. Perlmutter presented the AAEM conference with many possibilities for increasing our detoxifying potential. Quite a few have already been covered extensively in NOHA lectures and newsletters. Since the glutamate cascade is crucial in the destruction of neurons, a first step needs to be to avoid the ingestion of free glutamic acid (MSG), which is overwhelmingly prevalent in processed foods.2 (See, for example, NOHA NEWS, Spring 2000, "Free Glutamic Acid (MSG): Sources and Dangers.")

Dr. Perlmutter points out that antioxidants are essential in combating the oxidative stress to the neurons. As well as vitamins C and E, he mentions Coenzyme Q-10 as "one of the most promising agents for up-regulation of mitochrondrial function." "Phosphatidylserine [a form of lecithin, a phospholipid, which contains the amino acid serine3] enhances both neuronal and mitochrondrial stability and activity and reduces mitochrondrial free-radical production." A study at Stanford University School of Medicine showed learning and memory improvement in the majority of treated patients compared to controls. (See Lecithin lecture.3)

Dr. Perlmutter mentions acetyl-L-carnitine for increased cellular ATP production. (See The Carnitine Miracle4) "Apha-lipoic acid5 is emerging as one of the most promising agents for neuro-protection in neurodegenerative diseases. This potent antioxidant demonstrates excellent blood-brain barrier penetration. It acts as a metal chelator for ferrous iron, copper, and cadmium, and also participates in the regeneration of endogenous antioxidants including vitamins C and E, and glutathione."

"The lipophilic [fat-loving] antioxidant vitamin E is thought to play a major role in defending mitochondria against oxidative stress." Our October 2000 NOHA lecturer gave a fascinating presentation on "The Vitamin E Factor: The miraculous antioxidant for the prevention and treatment of heart disease, cancer, and aging. WHAT'S MISSING FROM YOUR VITAMIN E CAPSULE"6

The hormone melatonin has properties that could make it useful in neurodegenerative conditions. It is a free radical scavenger and increases the gene expression for powerful antioxidant enzymes. Melatonin is both lipid and aqueous soluble and easily passes the blood-brain barrier.7

Dr. Bland notes that this cascade with the uncoupling of mitochondrial energy production in the neurons and the release of unquenched oxidants "is observed not only in neurodegenerative diseases, but also with less severity in chronic fatigue syndrome, fibromyalgia, multiple chemical sensitivity, and in individuals with Gulf War Syndrome."

Dr. Perlmutter mentions a number of herbal medications that have been found to be helpful for neurodegenerative diseases. Some of them act by reducing the production of nitric oxide. As we know, the free radical nitric oxide with its unpaired electron is important for penile erection. (See NOHA NEWS, Fall 99, page 3, "Nitric Oxide.") When many toxic exposures put our immune systems in overdrive, we produce more nitric oxide (formula: NO) and the highly reactive oxidant-superoxide. When these two react together, they are most effective at the final killing of neurons. One researcher titled his article, "The Brain on Fire?"

Among the herbs mentioned by Dr. Perlmutter are silymarin (milk thistle), and Ginkgo biloba.

In his interesting introduction to Dr. Perlmutter's monograph for the AAEM meetings, NOHA Honorary Member Jeffrey Bland, PhD, praises Dr. Perlmutter highly and also gives a summary of the model presented by Dr. Perlmutter. Dr. Bland states that Dr. Perlmutter gives us "an integrated model of neurodegeneration coupling genetics, environment, nutrition, lifestyle, and infection." Agents triggering the cascade leading to the death of neurons in genetically susceptible individuals include toxins from the microorganisms in the gut, toxic metals and pesticides, food and environmental antigens, stress responses, and chronic infection. Dr. Bland notes that this cascade with the uncoupling of mitochondrial energy production in the neurons and the release of unquenched oxidants "is observed not only in neurodegenerative diseases, but also with less severity in chronic fatigue syndrome, fibromyalgia, multiple chemical sensitivity, and in individuals with Gulf War Syndrome."

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1See NOHA tape #165, "Detoxification and Healing-Key to Optimal Health" by Sidney M. Baker, MD, March 1998; and NOHA NEWS, "Detoxification and Healing," XXIII(4):1-3, Fall 1998.

2We have tapes and articles on the excitotoxins MSG and Aspartame. (The latter excitotoxin stimulates the exact same neuron receptors that are stimulated by glutamate. See Russell L. Blaylock, MD, Excitotoxins: The Taste that Kills: How Monosodium Glutamate, Aspartame (NutraSweet®) and Similar Substances Can Cause Harm to the Brain and Nervous System and Their Relationship to Neurodegenerative Diseases such as Alzheimer's, Lou Gehrig's Disease (ALS), and Others, page 28):

 
  • See NOHA tape #149, "Food Additives and Brain Damage (MSG and Aspartame) by Russell L. Blaylock, MD, November 1995;
  • See NOHA tape #112, "In Bad Taste: The MSG Syndrome," by George R. Schwartz, MD, September 1991;
  • See NOHA tape #120, "Aspartame (NutraSweet®): Is It Safe?" by H. J. Roberts, MD, October 1992;
 
 

and NOHA NEWS:

 
  • "The Doctor's Corner: Trick or Treat?" by Theodore E. TePas, MD, (A report on adverse reactions from aspartame: NutraSweet®), XV(4):2-3, Fall 1990 [link];
  • "Leaving a Bad Taste" (Review of In Bad Taste: The MSG Syndrome by George R Swartz, MD), XVI(1):3-4, Winter 1991 [link];
  • Aspartame (NutraSweet®): "The Need for Physician Whistle-Blowers in a Food Technology Revolution" by H. J. Roberts, MD, from his presentation at the 26th Annual Meeting of the American Academy of Environmental Medicine, XVIII(1):5-6, Winter 1993 [link];
  • "Excitotoxins: The Taste that Kills" (Review of Dr. Blaylock's book), XX(1):1-4, Winter 1995 [link];
  • "The Doctor's Corner: Danger: Not just taste enhancers!" by George E. Shambaugh, MD, (Describes the dangers and the deceptions surrounding the consumption of monosodium glutamate (MSG) and aspartame (NutraSweet®)), XXI(3):2-4, Summer 1996 [link];
  • "The Doctor's Corner: Attention Deficit, Hyperactivity, and Learning Disorders: A Scientific Appraisal of Dietary Therapies" by J. Gordon Millichap, MD, See the Section: ""Should aspartame and diet sodas be restricted in ADHD children?" XXIV(1):7, Winter 1999 [link];
  • "Free Glutamic Acid (MSG): Sources and Dangers" (Report on NOHA lecture by Jack Samuels plus a review of the article by Adrienne Samuels, PhD, on deceptions by The Glutamate Industry), XXV(2):1-4, Spring 2000 [link].
 
 
 
 
 
 

3See NOHA tape #178, "Lecithin and Health" by Frank Orthoefer, PhD, who described vividly the advantages to the brain from lecithins containing high amounts of the amino acid serine, April 12, 2000.

4See NOHA tape #173, April, 1999, "Nutrition Made Simple" by Robert Crayhon, MS, author of The Carnitine Miracle and NOHA NEWS, "Optimal Nutrition," XXIV(3):2-3, Summer 1999.

5See NOHA tape #175, "The Next Millennium Anti-Oxidant: The Alpha-Lipoic Acid Breakthrough," by Burton Berkson, MD, PhD, September 1999.

6See NOHA tape #182, "The Vitamin E Factor: The miraculous antioxidant for the prevention and treatment of heart disease, cancer, and aging," by Andreas Papas, PhD, November 2000.

7See NOHA tape #156, "The Melatonin Miracle," by William Regelson, MD, May, 1996.

Article from NOHA NEWS, Vol. XXVI, No. 1, Winter 2001, pages 6-8.