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I first became interested in alphalipoic acid (thioctic acid, ALA) in 1977, while I was an internal medicine resident in a Cleveland, Ohio, hospital. One October weekend, Mr. D, a patient suffering from acute hepatic necrosis, as a result of eating hepatotoxic mushrooms, was transferred to my care. The department Chief said that I was to observe the patient as a routine learning experience and I was advised that Mr. D. would probably die very soon. The Chief added that there was nothing that I could do but support him in the intensive care unit and watch.
Mr. D. was the sickest person I had ever seen. His laboratory values were several times normal and he had projectile vomiting and propulsive cholera-type diarrhea. Due to severe nausea, he could not find a comfortable position. He was miserable.
Normally, acute hepatic necrosis as a result of mushroom poisoning involves four stages. The person eats part or all of a poisonous mushroom and usually describes it as very tasty. Within 12 hours an acute and severe gastroenteritis sets in and the patient becomes dehydrated and electrolyte depleted. The third stage is an apparent recovery phase in which the patient is often released from the hospital in a weakened state. The weakness increases and within a few days, the patient falls into a coma, the fourth stage, and usually dies. I did not want this to happen to Mr. D. As a result of my Ph.D. education and my basic stubbornness, I did not accept the prognostications of the chief and began a search for a treatment that would reverse Mr. D’s condition.
Fortunately, I had remembered reading an article about a European drug that had been successful in the treatment of severe
1.Department of EPPWS (Applied Biology) G. Thomas Hall, New Mexico State University Las Cruces, NM 88003 (505)
liver damage while I was a mycology professor at Rutgers University. The drug, ALA, was stocked at NIH by Fred Bartter, MD who was chief of endocrinology. I called Dr. Bartter and he promptly shipped the ALA to me.
Thirty hours after Mr. D. had eaten the mushroom, the intravenous ALA was started. Within an hour, the patient said that he was feeling better. To everyone’s surprise, the patient continued to improve rapidly and was soon discharged from the hospital feeling fine and with almost normal laboratory values. The hospital chiefs told me that the patient’s recovery was an abnormality and not associated with the ALA therapy. They did not appear to be comfortable with the revival of the patient.
The following weekend, a young couple was admitted to the hospital after eating hepatotoxic mushrooms. Once again, these patients were assigned to me. I was ordered not to call NIH for more lipoic acid and to just support them medically with electrolytes and intravenous fluids. Both of the patients were deathly ill and suffered from the same symptoms as Mr. D. Their ALT and ASTs were in the hundreds of mμ/ml (showing signs of severe liver damage). I ignored the orders of the medical authorities and requested more ALA. Soon after the ALA was started, the couple showed an almost immediate improvement and within a short time they were feeling well with almost normal liver function.
Due to the amazing recoveries, NIH sent a team to Cleveland to examine my patients. I was delighted. I met Dr. Bartter and we started a long friendship and collaborative research arrangement. I was eventually awarded the FDA investigational drug permit for intravenous ALA. I thought Alpha-Lipoic Acid (Thioctic Acid)
the hospital chiefs would be happy with with the use of ALA15 and Ramakrishnan, what was taking place, but they were not. et al. showed that ALA could protect Since that time I’ve treated over a hundred hematopoietic tissue from free-radical patients with intravenous or oral ALA. In damage due to ionizing radiation.16 most cases, I have witnessed the same Numerous other studies have suggested amazing results. that ALA may be useful for the treatment of
diabetes mellitus. Haugaard, et al. demon-Alpha Lipoic Acid: The Molecule strated that ALA stimulated increased glu-ALA is a relatively small molecule with cose utilization in rat muscle cells17 and both hydrophilic and lipophilic character-Jacob, et al. reported that in humans, intraistics and a disulfide bond. It is a superb venous ALA significantly reduced insulin antioxidant and is an important coenzyme resistance.18 Estrada, et al., explained the for the production of acetyl coenzyme Al-increased glucose utilization by the fact that pha dihydrolipoic acid (DHLA) is the re-ALA stimulates glucose transport via the induced form of ALA and serves as an elecsulin signaling pathway.19 tron donor that recycles other important Neuropathies, a common complication antioxidants. For example, vitamin C is diof diabetes mellitus, results from a decrease rectly recycled by DHLA and in turn vitain blood flow to various organs. The actual min E is recycled by vitamin C. Glutath-neuropathic pain is caused by increased ione also appears to be recycled by DHLA.1 oxidative stress and a resultant impairment In addition, both ALA and DHLA have been of nerve function. Ziegler, et al. demon-reported to inactivate several harmful celstrated that over a 3 week period intravelular products of metabolism such as nous ALA produced a significant reduction peroxyl radicals,2 hydroxyl radicals3 and of neuropathic symptoms in 23 patients.20 singlet oxygen.4 Nagamatsu, et al. suggested that ALA ad
Furthermore, lipoic acid has been reministration accomplishes this by rendering ported to have metal chelating activity. harmless the products of lipid peroxidation Gregus, et al., demonstrated ALA’s chelating and by enhancing the entrance of glucose activity could be used to promote the ex-into the cell.21 cretion of mercury by the gall bladder5 and As a result of ALA’s lipophilic charac-Jayanthi, et al., reported that ALA can pre-teristics it can cross the blood-brain barvent calcium oxalate crystals from forming rier quite easily and plays an important role in rat renal tissue.6 In 1995, Ou, et al., de-in several neural metabolic processes. A scribed the chelation of copper by ALA7 number of authors have reported that ALA and veterinarians have known of ALA’s use and DHLA protected animals from neuroin the treatment of arsenic poisoning for nal death following laboratory-induced cermany years.8 ebral ischemia and reperfusion experi-
Recently there has been an explosion ments.22-24 Nagamatsu explained that this in disease-related ALA research. The drug protective effect was due to an ALA-in-has been shown to inhibit HIV replication duced rise in neuronal glutathione levels in cultured T cells,9 prevent cataracts of the which protected the nerve cells from the lens,10 protect the kidney from amino-harmful products of oxidation. glycoside damage,11 protect islet cells in the In Europe, ALA is often used as a treat-pancreas from inflammatory attack,12 in-ment for all types of liver disease. How-hibit thymocyte apoptosis13 and increase ever, as of yet, there is not a great amount helper T cells in the blood.14 Burger, et al. of scientific research on this subject and reported that the toxic side effects of vin-some studies have not produced positive cristine chemotherapy could be reduced results. In the case of Marshall, et al., ALA was not able to improve the course of the disease in 20 cirrhotic patients who did not stop drinking, but Marshall administered only 300 mg per day (very low doses) of oral ALA.25 In contrast to Marshall’s results, Loginov, et al., reported that ALA stimulated ATP production, enhanced hepatic regeneration and activated hepatic detoxification in 125 patients with chronic alcoholic and viral disease.26
Representative Alpha Lipoic Acid Case Histories
I have administered ALA, both oral and intravenously, to many patients, for several disease conditions, over the last twenty years. Three representative case studies are presented here. 1.Hepatitis C: Mrs. L. is a 36 year old woman who received a blood transfusion following the delivery of a normal female baby approximately three years ago. Several weeks after the transfusion, she developed a general malaise with myalgias and jaundice. She was easily fatigued and felt nauseated most of the time. Subsequent to a medical exam and blood work, she was diagnosed as suffering from hepatitis C. During the course of the disease the patient suffered pancreatic damage with resultant diabetes mellitus. These conditions were thought to be the result of multi-organ viral infection. The condition worsened and eventually a liver biopsy was performed and demonstrated acute and chronic hepatitis C with early cirrhosis. The patient’s gastroenter-ologist discussed interferon therapy and a possible liver transplant. The patient decided to try a alternative approach to this disease prior to any more complicated treatment.
When first examined in my office, Mrs L’s liver transaminases were elevated (AST was 168, ALT was 202) and she had a fasting blood sugar of 268. Her liver was tender and enlarged four finger breaths below the right costal margin and she was easily fatigued. For her diabetes, I prescribed 500mg of metforman twice a day and a low sugar and low calorie diet that was rich in vegetables. At the same time she was also started on 200mg of oral ALA three times a day, 300mg of silymarin three times a day, and 500 mg of pantothenic acid three times a day. Furthermore, an excellent multivitamin with B complex was started to supply the necessary thiamine as another coenzyme to the pyruvate dehydrogenase system.
The patient’s disposition started to improve by the second week and she reported a great increase in energy. Mrs. L. started back to college and by the eighth week, her fasting blood sugar had dropped to normal (112) and her liver transaminases continued to slowly fall (AST=122 and ALT=154). I am convinced that if Mrs. L. stays on her nutritional regimen, her healthy diet and practices stress management that she will continue to improve medically. 1.Diabetic Neuropathy: Mr. M, a 55 year old male, presented to my office two years ago with a fasting blood sugar of 203. He complained of burning and painful feet and paresthesias of his toes. He said that he had purchased several different types of shoes and shoe footpads, nevertheless his foot pain continued to increase. The diabetic neuropathy pain was not only interfering with Mr. M’s recreational activities, but also conflicting with his daily life and business operations.
Mr. M was put on a 2000 calorie ADA diet, a hypoglycemic agent (Glyburide 10mg twice a day), a good multivitamin and 600mg of oral ALA a day. Within five weeks the foot pain and toe paresthesias were gone and Mr. M was able to resume all of his normal daily activities without any discomfort. Mr. M has continued his ALA oral therapy and healthy lifestyle regimen and has been feeling healthy and free of neuropathies for two years. His most recent fasting blood sugar was 104.
Acute Hepatic Necrosis. Mr. P consumed several large Amanita mushrooms two days prior to his presentation at the first hospital emergency room. His symptoms were described as severe cramping with propulsive vomiting and diarrhea. He was treated with intravenous fluids, electrolytes, and an antiemetic and discharged. Twenty-four hours later, when his symptoms did not abate, he went to another hospital emergency room. Mr. P was hypotensive on presentation and was resuscitated with intravenous fluids and electrolytes. His liver function was gravely abnormal (ALT=3,125 mμ/ml) and his kidney function was poor. He was one of the majority of Amanita mushroom poisoning patients who develop acute hepatic necrosis.
Acute hepatic necrosis (massive and acute liver destruction) is a condition that may be caused by several agents such as carbon tetrachloride, fungal toxins or a large dose of an over-the-counter drug such as acetaminophen. The degree of liver damage that these poisons generate have been shown to be directly proportional to the quantity of the toxin and the period of time that the liver is exposed to the toxin. In time, if the person survives, fibrous tissue replaces the necrotic areas of the liver and transforms these regions into non-functional scar tissue.
During the course of acute hepatic necrosis, the injured liver cells release large amounts of transaminases (ALT and AST) and these laboratory values are indicative of the severity of the hepatic damage. Mr. P was admitted to the hospital and intravenous ALA was not started until his ALT was over 5,000 mμ/ml. By the third day of lipoic acid treatment, his ALT had dropped 1,500 mμ/ml and he said he was feeling much better. On the sixth post-therapy day Mr. P.s ALT was measured at 437mμ/ml and he was discharged from the hospital eighteen days later feeling normal, but weak, with an ALT of 79 mu/ml. A follow-up series of laboratory tests, one month following mushroom ingestion showed a normal ALT. Mr. P was just one example of over a hundred mushroom poisoning patients Alpha-Lipoic Acid (Thioctic Acid)
with acute hepatic necrosis who were successfully treated with intravenous ALA.
The Past and Future of Alpha Lipoic Acid
In 1980, Dr. Bartter and I published two papers describing our successes with ALA for acute hepatic necrosis using the NIH protocol.27,28 We expected a certain amount of interest in this remarkable new type of therapy, but we were disappointed in the lack of attention from the medical community. After Dr. Bartter’s death in 1985, I continued to study ALA as a therapeutic agent.
Today, in addition to my clinical practice, I am involved with a research program on the cellular effects of ALA in primates and I know of at least one well-respected medical center in the United States that is conducting a ALA research program on the treatment of diabetic neuropathies. I remain optimistic about the future of ALA and its ability to replace expensive and complicated treatments with a economical and more sensible method of treating several serious disease conditions.
Journal of Orthomolecular Medicine Vol. 13, No. 1, 1998
search, 1994: (Switzerland) 23: 365-370.
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