|Lipoic Acid: A blessing for diabetics Part I
An interview with Dr. Hans J. Tritschler
By Richard A. Passwater, Ph.D.
Part I Background
This is the first of two parts describing the benefits of lipoic acid supplementation and especially, the blessing benefits of lipoic acid for diabetics. Part I will provide the background, and part II will describe new studies showing the effectiveness of lipoic acid on improving glucose transport and utilization, regulating blood sugar levels, and reducing oxidative stress, the major risk factor for diabetic complications including neuropathy, retinopathy and cardiomyopathy.
I learned of Dr. Hans J. Tritschler's research with lipoic acid from Dr. Lester Packer. Dr. Tritschler and Dr. Packer had collaborated on a very interesting study that caught my interest. Dr. Tritschler has made several observations that shed new light into the relationship between the glycation and free-radical pathways that cause aging. He has also made many discoveries about lipoic acid and diabetes, energy production, muscle diseases and childhood diseases.
Glycation is the damage to proteins caused by sugar. Glycation causes damage very similar to that caused by free radicals. The damaged proteins are not only in muscle and organ tissues, but integral components of cell membranes and enzymes. The cellular membrane and enzyme damage leads to dysfunction, disease and cellular death.
In my book, "Chromium Picolinate: The Longevity Factor" (Keats Publishing, 1994), I discussed several synergistic relationships between glycation and free-radical damage, but Dr. Tritschler had uncovered a very important interrelationship showing how glycation products can cause the release of free radicals. We will discuss this later, but first we will examine the importance of lipoic acid for energy production and why lipoic acid has been used for nearly 30 years in Germany for diabetic neuropathy.
Dr. Tritschler's observations reported in several articles that Dr. Packer shared with me aroused my interest to learn more about Dr. Tritschler's research. A quick scan of the scientific literature revealed 50 articles ranging from diabetic neuropathy to mitochondrial myopathy. Dr. Tritschler received his Ph.D. in biochemistry from Philipps University at Marburg Germany and is the Specialist for antioxidants and metabolic compounds in the Department of Neurology of ASTA Medica AG in Frankfurt, Germany.
Passwater: Dr. Tritschler, during 1990 through 1992, while you were at the Columbia University College of Physicians and Surgeons, you published at least ten research articles dealing with mitochondria, cytochrome c oxidase and prions. You seemed to be concentrating on childhood diseases and muscle and energy disorders. What did you learn that then focused your research interest on lipoic acid?
Tritschler: During my stay at Columbia University I investigated the metabolic abnormalities causing neuromuscular disorders in infancy and childhood. Our group studied the biochemical abnormalities in the metabolic pathway underling these cytopathies. We found that alterations in the mitochondrial and nuclear encoded mitochondrion's proteins cause these neuromuscular disorders in infancy. The mitochondrion is the organelle for energy production within the cell. Therefore, a decline in the energy production represents the pathogenetic background of these disorders. This pathogenetic mechanism was later verified by NMR-spectroscopy. The abnormalities in the patients' muscles and brain are consequent to the insufficient levels of energy produced.
We also applied molecular biological methods to investigate the genetic background of these disorders. Several genetic abnormalities were found in the mitochondrial DNA, thus bolstering the hypothesis that the mitochondria's abnormalities constituted the biochemical bases of these disorders. Today we know that the mitochondrion is a very sensitive organelle and prone to alterations with related dysfunction that may underlie several other disorders like Parkinson's disease, and some forms of diabetes. However, in these disorders, the genetic and biochemical abnormality causes less severe dysfunction than in the neuromuscular disorders. After discovering the biochemical abnormalities of these neuromuscular disorders, we began investigating for the appropriate therapy.
Years later in Bologna, Dr. Rossella Medori and I treated these patients with lipoic acid, an important cofactor for the mitochondrial function. Surprisingly, we found that lipoic acid was improving the clinical conditions of these patients by increasing the brain energy levels. Using such therapeutic approach we showed for the first time that the mitochondrial cofactor lipoic acid may be successfully used in the treatment of disorders related to reduced energy levels.
Passwater: You have been welcomed into several prestigious laboratories around the world to collaborate -- Dr. Lester Packer at the University of California at Berkeley, Dr. Barry Halliwell at the University of London, Dr. Bruno Barbioli at the University of Bologna in Italy, Dr. Amira Klip at the Hospital for Sick Children in Toronto, Dr. Peter Nawroth at the Medical Clinic of the University of Heidelberg and Dr. P. L. Gambetti at Case Western University. You are a relatively young man and yet you have all ready achieved so much. From what I have observed, you are a six foot, five- or six- inch human dynamo -- both in scientific research and life. What has been your common research goal?
Tritschler: As a consequence of these findings, my research goal focused on the investigation of the mechanism or mechanisms underlying the function of lipoic acid. As many readers may already know from your book "Lipoic acid: The Metabolic Antioxidant" (Keats Publishing, 1995), this molecule has two biochemical functions. Firstly, lipoic acid plays a crucial role as a co-factor in the mitochondria with consequent ability to stimulate energy production.
Secondly, lipoic acid also has an antioxidant function. Surprisingly, this function has been overlooked for decades and has been only recently identified by Dr. Packer.
Hence, Professor Alt Bast in Amsterdam, Professor Packer at Berkeley and Professor Halliwell in London formed a research team with the common goal to investigate the antioxidant function of lipoic acid.
Oxidative stress is a general term applied to several different types of free- radical related cellular stresses. Investigating the antioxidant characteristics of lipoic acid in vitro, we found that it is a very strong antioxidant, capable of neutralizing every kind of free-radical attack. We are now in the process of evaluating the therapeutic potential in free radical disorders like diabetes and neurodegenerative disorders. Most recently, the therapeutic benefits of lipoic acid have been demonstrated in clinical studies of diabetic polyneuropathy which is also a disorder related to free radicals. This successful result is encouragement for further evaluation of the therapeutic potential of lipoic acid.
Passwater: At least eleven of your research papers have been co-authored with Dr. Packer, including the first of your reports on lipoic acid. What are the most interesting observations resulting from this collaboration?
Tritschler: The most interesting results of our collaborative efforts concern the antioxidant network theory. The antioxidant network consists of four different antioxidant molecules, in order to achieve global cell protection against free- radical attacks. The members of the network are the lipophilic (fat-soluble) antioxidant vitamin E and the hydrophilic (water-soluble) antioxidants
Vitamin C and glutathione.
The lipophilic antioxidant vitamin E protects the cell wall against oxidative stress, whereas the hydrophilic antioxidant Vitamin C and glutathione defend the interior of the cell against free radical attacks. Lipoic acid is the fourth and most important member of the antioxidant network. Because of its unique chemical structure, lipoic acid is able to interact with the lipophilic antioxidant vitamin E and the hydrophilic antioxidants vitamin C and glutathione. Without lipoic acid, the antioxidant network does not work efficiently, thus leading to cell damage.
We applied this therapeutical approach to several disease models related to oxidative stress such as cataract and HIV infection which are associated with decreased levels of Vitamin E or glutathione. Lipoic acid supplements enhanced the reduced levels of vitamin E or glutathione and overcame the oxidative stress by re-installing the disrupted antioxidant network. Because of this unique ability of lipoic acid, we sometimes call it the "antioxidant enhancer."
Passwater: You have presented several research reports on diabetic neuropathy at a conference on that subject held in Munich during March 17 through 19, 1995. I want to get to the new information that you presented there, but first, let's tell our readers a little about the use of lipoic acid in improving the diabetic's nourishment so as to reduce neuropathy. Lipoic acid is a coenzyme used by the body to help convert food into energy. Why is lipoic acid particularly important to the diabetic?
Tritschler: These recent results of lipoic acid therapy were presented at the international symposium in Munich which focused on the therapeutical effects of lipoic acid in diabetic polyneuropathy. A total of 30 speakers and 300 participants discussed the use of lipoic acid in the treatment of diabetes and diabetic polyneuropathy.
Peripheral neuropathy is a complication of diabetes leading to the loss of sensation in the limb extremities, trophic alterations and slow down of sensory and motor conduction velocities. This disorder is also associated with paresthesia (numbness) and pain in the advanced state. The pathogenesis of this disorder is very complex. Amongst the major pathogenetic factors, oxidative stress plays a crucial role in the damage of the peripheral nerve fibers. Professor Philip Low from the Mayo Clinic in Rochester, reported in Munich that lipoic acid is able to reduce oxidative stress in diabetic polyneuropathy and restore the impaired nerve function. These preclinical findings led to several clinical studies showing that a chronic daily treatment with 600 milligrams of lipoic acid induces the relief of symptoms in diabetic polyneuropathy. Another large clinical trial including 260 patients has also shown improvement of nerve function such as increased sensation in the lower limbs. Moreover, an improvement of cardiac function was observed in another trial investigating diabetic patients with heart dysfunction due to autonomic neuropathy.
Passwater: Lipoic acid has been used in Germany for decades to help diabetics. There are obviously clinical studies as well as case histories to support the use of lipoic acid as a nutritional adjunct in the treatment of both type I and type II diabetes. Why are the benefits of lipoic acid known and taken advantage of in Germany, but only the holistic practitioners in the U. S. seem to be aware of these benefits of lipoic acid?
Tritschler: This is a very good question. Lipoic acid has been used in Germany for over 25 years in the treatment of diabetic polyneuropathy. The clinical use was done on an empirical base for the last 20 years. This means that doctors prescribed this nutrient in spite of the lack of clear efficacy demonstrated through a well designed controlled clinical study in diabetic polyneuropathy. The results I have mentioned above are from this last year and have been presented only recently at international meetings. Therefore, the international medical society has not been aware until lately of lipoic acid treatment for diabetic polyneuropathy.
Passwater: Does lipoic acid stimulate muscle ATP production? What does this mean to a diabetic or healthy person?
Tritschler: Yes, lipoic acid stimulates muscle ATP production during exercise. This has been shown recently in diabetic patients by means of NMR-spectroscopy. Since ATP is necessary for muscle function, an increase in ATP production should lead to better muscle performance. We have performed these measurements in diabetic patients, however we can only hypothesize a somewhat similar result in healthy individuals until these studies are completed.
Passwater: Does lipoic acid work by converting blood sugar into body fat, or does most of the glucose go towards energy production? If so, is this in diabetics only or in healthy people as well?
Tritschler: Professor Packer and Professor Nawroth from Heidelberg have shown that lipoic acid can reduce glycation. This observation is of pivotal importance, since the glycation process represents the initial pathological event leading to the diabetic complications such as nephropathy, polyneuropathy, microangiopathy and others.
Passwater: What evidence have you seen that lipoic acid reduces glycation?
Tritschler: There is a large amount of evidence showing increased oxidative stress in association with diabetes. We have just concluded a multicenter study that shows that 600 milligrams of lipoic acid daily reduces oxidative stress in diabetics. Since oxidative stress is a risk factor of diabetic complications, this further establishes the efficacy of lipoic acid for diabetics. Furthermore, we have shown that lipoic acid improves glucose utilization and oxidative stress.
For more on this interesting topic, read "Part II Lipoic Acid: A blessing for diabetics".
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