Alpha-Lipoic Acid and Liver Disease
by Burton M. Berkson MD, MS, PhD
Alpha-lipoic acid (ALA, thioctic acid, pyruvate oxidation factor) was first discovered by bacteriologist Irwin C. Gunsalus in 1948, when he observed that aerobic (oxygen-requiring) bacteria could not grow without it. Later, Gunsalus and Lester Reed determined the true structure and named it ALA (1951). ALA is a natural substance, produced in every higher-type cell, and it has many functions. Probably most important, ALA is the rate-limiting factor for the production of energy from carbohydrate (pyruvate). Without ALA, you could not obtain energy from the food you eat, and you could not stay alive.
ALA is also an excellent antioxidant and recycles other nutrients such as coenzyme Q10, vitamin C, and vitamin E. In addition, ALA chelates heavy metals such as mercury, lead, and arsenic; and it stabilizes NF kappa B transcription factor so that it helps to inactivate deleterious genes. It can also help people with diabetes mellitus by increasing the sensitivity of their cells to insulin, and it helps reverse diabetic neuropathies.
The first large human clinical studies using ALA in the US were carried out in the 1970s by Drs. Fredrick C. Bartter, Burton M. Berkson, and associates from the National Institutes of Health. They administered ALA to 79 people with severe and acute liver damage at various hospitals around the US, and 75 recovered full liver function.
Dr. Bartter and I were appointed by the FDA as principal ALA investigators, and I went on to use it successfully for the treatment of chronic liver disease. In combination with low-dose naltrexone, I have used ALA to treat various cancers for which no other treatment exists. (For more information, readers might want to go to PubMed and type in “liver,Berkson.”)
My first experience using antioxidant therapy was in 1977, when I was an internal medicine resident. A man was poisoned and suffering from acute liver failure. His liver function tests were in the thousands of mg/dL, and he had propulsive diarrhea, projectile vomiting, and dreadfully painful muscle spasms throughout his body. He was the sickest person that I had ever seen. Due to the relentless muscle cramping and pain, he could not find a comfortable resting position. One of the department chiefs told me that nothing could be done to save his life except for an immediate liver transplant; however, a donor liver was not available. I was ordered to administer medical support and to just observe the patient as he went though the phases of death. I was told to take notes and prepare a report for grand rounds at the hospital.
Death from liver necrosis usually involves four separate stages: (1) ingestion of a poison, such as acetaminophen, a poisonous mushroom, hepatotoxic hydrocarbon solvent, etc.; (2) development of acute and difficult gastroenteritis with dehydration, pain, and electrolyte depletion; (3) a noticeable recovery phase in which the patient is often released from the hospital in a weakened state; and (4) increased weakness followed by coma and death. Because I did not want to see this happen to my patient, I began a search for a way to reverse his condition.
Fortunately, I remembered reading an article about a new drug that had been shown to be helpful in the treatment of severe liver damage. The drug, alpha-lipoic acid (ALA) was stocked at the National Institutes of Health (NIH) by Fred Bartter, MD, the chief of endocrinology. Dr Bartter was interested in this agent because he thought that because it lowered blood sugar levels, ALA might be used as a drug for diabetes mellitus and its complications.
About 30 hours after my patient had ingested the deadly toxins, the intravenous (IV) ALA was started. Within a few hours, the patient began to feel better. We were all surprised that he continued to improve, and he was soon discharged from the hospital with nearly normal laboratory values and feeling a little tired, but normal. He is still well and free of liver disease, 30 years later.
After I treated three more patients with severe liver damage with ALA and obtained the same remarkable results, most of the hospital chiefs were still skeptical; however, Dr. Bartter and I were delighted. NIH sent a team of doctors to Cleveland to examine my patients, and I was eventually awarded the FDA investigational drug permit for the use of IV ALA. Dr. Bartter and I published three papers describing our successes with IV ALA, and we expected a certain amount of interest in this remarkable organ-regenerative protocol. We were disturbed by the lack of attention from the American medical community. Dr. Bartter died in 1985, and I continued to study ALA as a therapeutic agent and as a nutraceutical.
Since my work with Dr. Bartter, I have treated hundreds of patients with IV and oral ALA for acute and chronic liver damage, autoimmune disease, cancer, etc., along with other interesting agents with promising results. Below are a few case studies of hepatitis C taken from my office practice.
In my opinion, there are four laboratory tests that really tell a doctor what is going on in the liver. The first is the platelet count. It is important because, as liver inflammation and scarring progress, the platelet count goes down. So the platelet count is a very helpful indirect indicator of liver health, and a rise in platelet count is an indication of a healing liver.
I believe that the albumin level is the most important liver function test. A diseased liver can only produce a small amount of albumin. So a person with severe liver disease has a low albumin level, and as the liver improves, the albumin level rises.
The ALT is a liver enzyme that results from damage to the liver. It normally goes up and down from day to day, however, a downward trend may suggest an improvement of liver function. Interestingly enough, in cases of severe liver disease, the ALT is very low because most liver cells have been killed off.
The prothrombin time (time it takes the blood to clot) is a very important tool for measuring liver health, because a sick liver cannot produce much of the clotting factors, and thus the prothrombin time is elongated in severe liver disease. As the liver regenerates, the prothrombin time shortens.
Case 1
Mr. CA, a 68-year-old salesman from Ohio, was infected with hepatitis C, following a blood transfusion in the hospital. Soon afterwards, he became ill and was found to have hepatitis C. He was sent to a hepatologist, who immediately put him on interferon and ribaviron, which made him feel as if he had influenza for several months, and the drugs ultimately damaged his bone marrow. After the failure of interferon/ribaviron, Mr. CA was told that nothing could be done other than liver transplantation.
Mr. CA presented to my office suffering from fatigue, anxiety, anemia, and abdominal pain and distension (ascites). I treated him with my triple antioxidant therapy (ALA, selenium, and silymarin). Within a short time he began to feel normal and was free of the signs and symptoms of liver disease. Below are some of his results (Figures 1, 2, 3, 4).
Figure 1
Figure 2
Figure 3
Figure 4
Case 2
Mr. EA, a 54-year-old man from California, was infected with hepatitis C during a blood transfusion following surgery. He did not feel well for several years following surgery, and his physician did some laboratory tests that demonstrated hepatitis C. A liver biopsy showed moderate cirrhosis with active inflammation.
Mr. EA presented to my office with fatigue, anxiety, abdominal pain, and some ascites. His ALT was elevated, and his viral load was elevated by the Chiron PCR method. I treated him with my triple antioxidant therapy, and within a few months, he started to feel normal. Some of his results are illustrated below (Figures 5, 6, 7, 8).
Figure 5 Platelet Count
Figure 6
Figure 7
Figure 8
Case 3
Mrs. KVP is a 40-year-old woman in excellent health who developed hepatitis C from a blood transfusion following surgery. Her family doctor sent her to a liver expert who told her that she was seriously ill and must be treated immediately with interferon and ribaviron. KVP had no complaints and had heard that the standard treatment often made people much sicker than doing nothing.
KVP presented to my office, and her blood tests were all normal, except her ALT liver enzyme was elevated at about 300 mg/dL. This indicated that there was viral activity and inflammation in her liver. KVP’s original laboratory tests and her progress after being treated with my triple antioxidant therapy over three years are demonstrated in the following charts (Figures 9, 10, 11, 12, 13 ).
Figure 9
Figure 10
Mrs. KVP
Albumin Level
Figure 11
Figure 12
Figure 13
MRS. KVP
After three years, she once again visited her hepatologist, who told her that actually that she was getting sicker because her viral load had increased dramatically (Figure 12 ). Again he said that she should be put on interferon and ribaviron and be evaluated for a liver transplant. Incidentally, she had great health insurance.
Mrs. KVP is a health professional and questioned her hepatologist. She asked him if the original viral load was acceptable. He said yes; however, it had increased from 600,000 to 6,000,000 units, which showed progression of her disease. She asked him if he knew that the first viral load tests were done by the Chiron method and the second tests were done by the Quantasure method. He did not know that. Then, she told him that viral load is an artificial exaggeration (amplification) of the amount of viruses by millions, and the Quantasure method appears to amplify the amount of viruses by ten times more than the Chiron method. After hearing this reasonable explanation, he answered that viral load was not a very important test anyway.
The three people described in this study continued to stay on the triple antioxidant therapy, and I still see two of them as patients today (fall 2007). The two continue to improve. I added silymarin and selenium to ALA for my triple antioxidant therapy, because these agents also protect the liver from free-radical damage, regenerate the other fundamental antioxidants, and interfere with viral replication. Although my first acute hepatic necrosis patients were treated with ALA alone and did exceedingly well, all the patients presented in this article followed the triple antioxidant program and recovered quickly from their illness.
The standard of care treatments for severe liver damage, especially liver transplant surgery, can be painful, disabling, and extremely costly. From my practice experience, interferon and antivirals have less than a 30% improvement rate, and this response is usually not permanent. Liver transplant surgery in a few cases can be lifesaving and necessary, but is uncertain and tentative, partly due to the residual viremia that ultimately infects the newly transplanted liver. I have found that the highest viral loads are following liver transplant surgery, since the residual viruses in the bloodstream and tissues have a new healthy liver to feed on.
The triple antioxidant therapy offers a more conservative approach to the treatment of hepatitis C that is much less expensive. One year of antioxidant therapies described in this paper costs only a few thousand dollars, whereas liver transplant surgery costs more than $400,000 a year, and in five years, the person will probably require a new transplant. And, in addition, the transplant patient will require antirejection drugs and many doctor and hospital visits. It appears reasonable to me that before transplant evaluation or during the transplant evaluation process, this conservative triple antioxidant treatment program should be considered. If there is a significant improvement in the patient’s condition, liver transplant surgery may be avoided.
Not too long ago, I was invited by the Internal Medicine Society of Saxony to present my triple antioxidant protocol to the group in Dresden, Germany. I was asked why viral loads did not always fall to very low levels with my treatment program. I answered that, from a microbiologist’s point of view, I did not believe that one could ever completely eradicate a viral disease without killing the patient. I added that we could only hope to support and “teach” the immune system how to recognize and control a virus. Normally, viruses remain part of our biology for the rest of our lives. And this does not necessarily make a person sick. We are all filled with billions of dormant viruses. As long as we have a healthy lifestyle and avoid unnecessary emotional and physical stress, the viruses should remain dormant. I believe that one can live to 100 years old with hepatitis C and still be a healthy person.
Burton M. Berkson, MD, MS, PhD
1155 Commerce Drive, Suite C
Las Cruces, New Mexico 88011
505-524-3720
Selected Alpha-Lipoic Acid References
Bartter FC, Berkson B, Gallelli J, Hiranaka P. Thioctic acid in the treatment of poisoning with alpha-amanitin. In: Faulstich H., Kommerell B, Wieland T, eds. Amanita Toxins and Poisonings. Baden-Baden: Wizstrock; 1980:197–202.
Baur A, Harrer T. Alpha lipoic acid is an effective inhibitor of human immuno-deficiency virus (HIV-1) replication. Klin Wochenzchr. 1991;69:722–724.
Berkson B. Thioctic acid in treatment of hepatotoxic mushroom poisoning. N Engl J Med. 1979;300:371.
Berkson B. Treatment of four patients with thioctic acid. In: Faulstich H, Kommerell B, Wieland T, eds. Amanita Toxins and Poisonings. Baden-Baden: Wizstrock; 1980:203–207.
Berkson BM. Alpha-lipoic acid (thioctic acid): my experience with this outstanding therapeutic agent. J Orthomol Med. 1998;13:1:44–48.
Berkson BM. A triple antioxidant approach to the treatment of hepatitis c using alpha- lipoic acid (thioctic acid), silymarin, selenium, and other fundamental nutraceuticals. Clin Pract Altern Med. 2000;1:1,27–33.
Berkson BM. A conservative triple antioxidant approach to the treatment of hepatitis c. combination of alpha-lipoic acid (thioctic acid), silymarin and selenium. Three case histories. Med Klin. 1999; 94(3): 84–89.
Berkson BM, Rubin D, Berkson AJ. Long-term survival of a 46-year-old man with pancreatic cancer and liver metastases and treated with intravenous alpha lipoic acid and low dose naltrexone. Integr Cancer Ther. March 2006; 5(1):83–89.
Berkson BM, Rubin D, Berkson AJ. Reversal of signs and symptoms of a B-cell lymphoma in a patient using low-dose naltrexone. Integr Cancer Ther. 2007;Sep;6(3):293–296.
Burkhart V, Koike T, et al. Dihydrolipoic acid protects pancreatic islet cells from inflammatory attack. Agents Actions. 1993;38:60–65.
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Cao X, et al. The free radical scavenger alpha-lipoic acid, protects against cerebral ischemia-reperfusion injury in gerbils. Free Radic Res. 1995;23:365–370.
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Estrada D, Ewart H, et al. Stimulation of glucose uptake by the natural coenzyme alpha lipoic acid. Diabetes. 1996;45:1798–1804.
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Grunert R. The effect of DL-alpha lipoic acid on heavy metal intoxication in mice and dogs. Arch Biochem Biophys. 1960;86:190–195.
Haugaard N, Haugaard E, et al. Stimulation of glucose utilization by thioctic acid in rat diaphragm incubated in vitro. Biochim Biophys Acta. 1970;222:583–586.
Jacob S, Henriksen A, et al. Enhancement of glucose disposal in patients with type 2 diabetes by alpha-lipoic acid. Arzneimittelforschung/Drug Res. 1995;45:872–874.
Loginov AS, Nilova TV, Bendikov EA, Petrakov AV. Pharmacokinetics of lipoic acid preparations and their effects on ATP synthesis, processes of microsomal and cytosole oxidation in human hepatocytes during liver damage. Farmacol Toksikol. 1989;52:78–82.
Nakai S. Liver function promoting agents by experimental liver perfusion. I. Effect of thioctic acid on the detoxifying function of the liver. Chem Abst. 1960;54:11274.
Nagamatsu M, Nickander, K. Lipoic acid improves nerve blood flow, reduces oxidative stress, and improves distal nerve conduction in experimental diabetic neuropathy. Diabetes Care. 1995;18:1160–1167.
O’kane DJ. Gunsalus IC. Pyruvic acid metabolism: a factor required for oxidation by streptococcus faecalis. J Bacteriol. 1948;56:499–506.
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Prehn JH, Karkoutly, et al. Dihydrolipoic acid reduces neuronal injury after cerebral ischemia. J Cereb Blood Flow Metab. 1992;12:78–87.
Ramakrishnan N, et al. Radioprotection of hematopoietic tissues in mice by lipoic acid. Radiat Res. 1992;130:360–365.
Sandhya P et al. Role of DL alpha lipoic acid in gentamycin-induced nephrotoxicity. Mol Cell Biochem. 1995;145:11–17.
This article orginally appeared in our December 2007 issue.
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