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Lipoic Acid Breakthrough
By Richard A. Passwater, Ph.D.
In the March 2003 column on Syndrome X, I mentioned that I had been chatting with Dr. Burt Berkson about alpha lipoic acid (ALA) and planned to share our conversation with you because of its importance. I wish that I could write two columns a month so that I could bring you important news more quickly.
Burt Berkson, M.D., Ph.D. practices nutritional and integrative medicine in Las Cruces, NM, and is an adjunct professor of applied biology at New Mexico State University. He has been a lecturer, researcher, and professor at several institutions including the Max Planck Institute, University of Illinois and Rutgers University at Newark and New Brunswick, NJ. In addition to being an M.D., he has an M.S. in biology and a Ph.D. in cell biology. Recognized as one of the leading experts on ALA, Dr. Berkson is an active writer and speaker with numerous published works in scientific, medical and popular journals. He is the author of The Alpha Lipoic Acid Breakthrough (Prima Publishing, 1998). He was for 23 years the principal FDA investigator for its intravenous use and a consultant to the National Centers for Disease Control and Prevention.
Passwater: Why did you decide to study medicine years after earning your doctorate in cell biology?
Berkson: I was accepted to medical school in Chicago a short time after I graduated from college, however, I did not go to medical school. I just wasn’t interested in assuming the responsibilities of an M.D. at that time.
Instead, I started graduate school. After earning a masters degree, and a Ph.D. from the University of Illinois in Urbana, I took an assistant professorship Rutgers University.
Being a professor was very enjoyable; however, I was on several university medical school committees and slowly developed an interest in clinical medicine. As a 33year-old associate professor, I was very content, but my wife was having repeated miscarriages and that was very stressful. At that time I believed that if we visited distinguished university heads of departments that we would get the best medical advice and treatment. We visited several “experts” and received the same information from every one of them. It appeared that these people did not think independently, but rather behaved like robots, each of them, hypnotic trance-like, repeating the same advice to everyone.
Frustrated, one day I went to the obstetrics library at the university and looked up scientific papers on repeated second-trimester miscarriages. There was an East Indian publication that said that if a woman has a miscarriage with a D and C, sometimes the cervix may become lacerated and she could develop an incompetent cervix. The doctor described a treatment for this condition using a purse-string ligature. When I presented this information to the “experts,” they told me that I should not practice obstetrics without an M.D. and completion of a residency program. They completely ignored the new information that I presented to them and repeated the same meaningless advice.
Then one day in the library, I saw a scientific paper by a student of the Indian doctor and he was practicing in New York City. Soon after my wife got pregnant, we visited Dr. Clyman and he said that I was correct. He surgically inserted the ligature and she carried the baby to full term without any problems. She delivered a healthy baby girl. Within a short time my wife became pregnant again and we did the same thing. My wife delivered a healthy baby boy. Today, this ligature procedure is well accepted, but 35 years ago it was not part of the “cookie-cutter” protocols.
Because of these experiences, and others with family members, I thought that in order to get good medical care one had to be part of that system. So you see why as a medical doctor I am always open to new ideas and why I regularly question accepted medical protocols.
Passwater: Yes. So what was next?
Berkson: The University of Miami was offering an accelerated Ph.D. to M.D. program, but the classes were filled years in advance. Consequently, I wrote a letter to the Universidad Autonoma de Guadalajara and asked them if they would allow me to finish my two clinical years in the hospital since I had already taken the pre-clinical years. I wrote that I would teach their students medical microbiology. They said yes. So, I moved my family to Mexico and started teaching and studying. There were 25 other American medical school professors in the program with me.
To make a long story shorter, a group of doctors and administrators representing teaching hospitals in Cleveland and Connecticut came down to visit us in Mexico and offered us the same program in the United States if we taught their students and residents our areas of expertise. And there was a salary, too. So, I took the offer and moved my family to Cleveland where I finished my medical education.
So, the M.S. and Ph.D. were first, and the M.D. was second. I think that this sequence of degrees gave me some very special insights into the practice of medicine.
Passwater: You’re the world expert in several aspects of lipoic acid (ALA) research and its clinical use. What led you to alpha lipoic acid?
Berkson: While working as an internal medical resident at one of the Case Western Reserve teaching hospitals in 1977, I was asked by the chief to follow two patients with severe and acute liver damage that resulted from eating hepatotoxic mushrooms. This condition is often fatal and I was told that the patients would most probably die.
As a medical doctor it was necessary to follow the orders of the chief; however, as a PhD, I sought new ways of doing things. I called Dr. Fred Bartter (former chief of endocrinology) at the National Institutes of Health and asked him if he knew of anything that would help regenerate damaged organs. He answered that he was working with thioctic acid (alpha lipoic acid, ALA) and it seemed to help heal damaged livers and other organs. In addition, he said that he thought that ALA might also have a positive effect on pre-diabetes (metabolic syndrome, syndrome X).
Dr. Bartter sent me a case of ALA for intravenous administration. I picked it up at the Cleveland airport about seven hours after I initially called him. I rushed back to the hospital and injected the ALA into the two patients. I administered this treatment every six hours for 14 days. The patients started to recover and felt much better by the second day and were able to leave the hospital within two weeks with normal liver function. They are still alive and free of liver disease today, 28 years later.
It is interesting to note that some of the chiefs at the hospitals where I practiced medicine seemed to discourage my use of ALA. I was told that with an M.D., and a Ph.D. in mycology, and internal medicine training, I should concern myself with doing infectious disease research and stay out of liver disease.
Dr. Bartter, however, thought our work was very important and told me that some day we might win a Nobel Prize for our human work with ALA. He suggested that I leave Cleveland and come to work with him. But I was very discouraged by the response that I experienced from the medical community in Ohio. I left the region and moved my family to a rural community not too far from Lubbock, TX.
I became a country doctor, driving from one hospital to another each day, and even delivered babies in people’s houses on isolated ranches. My children went to school there and received a very good basic education. Nevertheless, when they were high school age we moved back to a relatively large city. There, I first became introduced to “managed care” medicine. I didn’t like this approach and was fortunate to land a job at White Sands Missile Range and Research Facility near Las Cruces, NM, where I had some interesting experiences. About eight years ago, I opened a small integrative medical practice in Las Cruces where I use antioxidants and certain innovative prescription drugs to treat diabetes, chronic hepatitis, rheumatoid disease, lupus, and other disorders with exceptionally good results.
Passwater: What does ALA have to do with overcoming liver failure?
Berkson: ALA’s physiological actions are the keys to overcoming liver failure.
Passwater: What are the functions of ALA?
Berkson: First, ALA is the rate-limiting factor for the production of acetyl coenzyme A, the fuel for the mitochondrion. So, increased ALA means more efficient mitochondrial effectiveness and healthier hepatocytes.
Second, with any serious organ disease, there is a reduction in glutathione. Glutathione, as you know, is the most efficient intracellular antioxidant and removes so many harmful products of inflammatory organ damage. ALA is the most efficient generator of intracellular glutathione.
Third, ALA by itself is a very efficient free radical scavenger and removes many inflammatory products that interfere with normal organ regeneration.
Fourth, ALA has been found to stabilize nuclear transcription NF kappa B. NF kappa B is an intracellular promoter of inflammation and cellular damage. So, ALA appears to slow many inflammatory processes.
Fifth, I think that ALA has a direct effect on stem cells and stimulates them to divide and differentiate into normal liver cells thus repairing damaged organs.
Sixth, several antioxidants work in the cell to help scavenge the free radicals that damage tissue. When vitamin C, vitamin E, coenzyme Q-10, etc. are used up, ALA can regenerate them and make them effective once more.
Passwater: What other success stories with ALA did you have early on?
Berkson: Dr. Bartter and I, with others, published two papers on 79 people with potentially fatal acute liver disease at various medical centers around the country in 1980. The studies were published out of NIH. Using just intravenous ALA, 75 of the 79 survived.
One day about 25 years ago, I got a referral from an internal medicine doctor who had a relative with primary biliary cirrhosis. There was no effective treatment for this chronic liver disease and he thought that maybe I might know something about how to treat this woman.
If ALA worked for acute liver disease, would it not be effective for chronic liver disease? I administered the ALA and the woman’s laboratory values quickly improved. Then I started treating patients with hepatitis B, autoimmune hepatitis, and hepatitis C with the same great results.
Passwater: You often prefer to give ALA intravenously rather than orally. What’s the difference?
Berkson: When a person absorbs oral lipoic acid it goes directly to the liver first where it is used for various purposes. Very little pure ALA, or its reduced form DHLA, actually enters the bloodstream. When ALA is administered intravenously it travels to the brain, heart, liver, pancreas, lungs, etc. in a rather pure form to do its work. When a person has a chronic disease he actually has a disorder of oxidative stress with free radicals potentially damaging all of his tissues. Therefore, a person with diabetes would benefit from oral ALA, but might do better in the long run with intermittent intravenous treatments.
I don’t do blood levels of ALA. I just assume that a person with a chronic disease is in need of an excellent free radical scavenger. Years ago, I did do extensive esoteric laboratory workups, but most patients complained about the excessive costs and the fact that insurance companies did not pay for these tests.
Passwater: Is this what led you to become the principal FDA investigator for the intravenous use of ALA?
Berkson: Yes. Nonetheless, there was almost no interest by the American pharmaceutical companies.
Passwater: How did this lead to you becoming a consultant to CDC on ALA?
Berkson: Some people at the CDC were familiar with my work with liver regeneration using ALA and asked me to be a consultant.
Passwater: Why did you write your book, Alpha Lipoic Acid Breakthrough? What was your message?
Berkson: Over the years, I became discouraged by the lack of interest concerning ALA by the medical and scientific communities. I thought that writing a popular book on the subject would generate interest in this remarkable natural agent. I think that my book along with other books such as your 1995 book on the subject did just this.
Passwater: In your book, you discuss how ALA can slow the aging process and that endogenous ALA declines with age. Please elaborate on the relationship between aging and endogenous ALA production.
Berkson: The first published research on anti-aging with ALA was done by the Germans from the 1970s to the early 1990s. In 1991, Dr. von Zglinicki and his group demonstrated that ALA (thioctic acid) could prevent damage to aging mitochondria and Dr. Stoll and his team showed that ALA improved memory in aging mice. Then, in 1994, Dr. Stoll and his colleagues in a New York Academy of Science article reported that ALA could improve cognition in rodents. Later, Dr. Freisleben and his crew demonstrated that ALA along with other antioxidants could prolong survival time in immunosuppressed mice by up to 200%.
Much of the early research was supported by the German pharmaceutical company Asta Medica. Asta Medica was one of the first European manufacturers of prescription ALA. In the mid 1990s Dr. Hans Tritschler, a representative of Asta Medica and Dr. Claus Gehringer (the former president of Asta Medica) came to America to encourage and support ALA research at various American institutions. Much of the consequent biochemical work was done at the University of California at Berkeley by Dr. Lester Packer’s group.
Passwater: Dr. Tritschler was kind enough to discuss ALA and diabetes with us in the June and July 1996 columns. ALA is a blessing to diabetics. Do we have animal studies that support the concept that replacing and/or supplementing with ALA slows aging?
Berkson: In the late 1990s, Dr. Bruce Ames’ group at Berkeley showed that supplementing lipoic acid to old rats could improve the indices of metabolic activity and lower the oxidative stress and damage that accumulates in the aging process. They found that feeding old rats large amounts of acetyl carnitine and lipoic acid restored their mitochondrial function and lowered their oxidants to the level of a young rat. As a result the old rats appeared to become more youthful and had increased ambulatory activity. Dr. Ames concluded that these two metabolites can be considered necessary for a healthier old age. This restoration of increased ambulatory activity suggested a reasonable mechanism by which age-increased oxidative damage to cellular structures might be reversed with ALA and acetyl carnitine.
In my practice, I regularly see the same amazing results every day with older humans.
Passwater: Dr. Ames described some of his research with ALA and mental rejuvenation for us in October and December 2002 columns. You also discuss ALA as a cancer preventer/fighter. Please comment.
Berkson: ALA appears to be rather toxic to cancer cells. In my practice, I often see people with metastatic cancers who have tried all of the standard therapies at major medical centers and are told that there is no hope for survival. Many are told that they have only a few months to live. When they arrive here, they are very depressed and want to know ways to make their last few months less painful. I tell them that I can promise no miracles, but that a positive outlook, healthy diet, and good antioxidant supplements may help make them feel better.
Let me give you a specific example. Mr. N.M. is a 46-year-old man who developed pancreatic cancer with metastases to his liver. One of the most prominent cancer treatment centers told him after a full treatment regimen that he would certainly die within a few months. I started him on our program plus intravenous ALA. He is now feeling and looking normal after two and one-half years, and he is back at work without any complaints. Periodically, we do CT scans and PET scans. The primary cancer and metastatic cancers are still there, but they appear to be shrinking and seem to be rather dormant. I’m preparing a publication on this case.
Passwater: Why would ALA discourage the growth of cancer?
Berkson: First of all, most cancers appear to prefer a rather anaerobic environment. ALA promotes aerobic respiration. Second, most cancers require the separation of an inflammatory transcription factor in order to pass information to the damaged genetic material. ALA has been shown to stabilize various transcription factors and discourage the growth of mutated cells.
Passwater: What is the relationship between ALA and glutathione, and why is this important?
Berkson: Glutathione is an indispensable antioxidant that is synthesized within the mitochondrion. I don’t think that it can be reliably augmented by oral administration because it cannot always pass over the membranes as glutathione. So glutathione must be synthesized within the mitochondrion.
Glutathione removes the free radical waste products that result from normal metabolism and the toxins produced by alcohol consumption, cigarette smoking, cancer chemotherapy, various drug byproducts, and exposure to harmful radiation. Because glutathione protects our cells from free radical damage, it protects the tissues, organ systems, blood vessels, nervous system, immune system, liver, heart, lungs, kidneys, etc. against damage.
Glutathione is a component of certain enzyme systems that protect us from organ damage. So, patients with serious diseases usually have their glutathione depleted. Enzymes such as glutathione peroxidase and glutathione transferase require large amounts of glutathione to protect our tissues against several deadly toxins.
As I said, glutathione does not usually perform well when taken by mouth. Then what can be done to raise endogenous glutathione levels? Several studies have shown that ALA and its reduced state, dihydrolipoic acid (DHLA), can stimulate the cell to generate significantly higher levels of glutathione. An example of this can be seen with AIDS patients who have very low levels of glutathione due to the constant very high levels of metabolic stress in their tissues. The oxidative stress stimulates the replication of the HIV virus. Glutathione and its precursor, ALA, can prevent the replication of these viruses by scavenging the numerous free radicals and consequently lowering oxidative stress.
Passwater: You mentioned that ALA has been studied in diabetes and we have chatted earlier about Syndrome X (March 2000). What is the mechanism here? It’s not its antioxidant properties.
Berkson: In the 1970s when I first talked with Dr. Fred Bartter, he thought that ALA might one day be used as a drug to control diabetes since it gently lowered glucose levels when given to patients in rather high doses. Dr. Bartter wasn’t sure how it worked, but he thought that it might somehow change the insulin receptor in the metabolic syndrome or pre-diabetes (Syndrome X).
Over the last 28 years, I have treated hundreds of patients with diabetes and its complications. I am still amazed when a man comes shuffling in on his first visit, due to painful feet from diabetic neuropathies, and after a few months of therapy, the same person can walk normally.
Passwater: Has this been shown to help patients having diabetic neuropathy or diabetic retinopathy?
Berkson: Let me give you an example. A few years ago, a religious leader and corporate head from Africa was visiting a university medical center in Washington, DC for his diabetic neuropathies and retinopathies. He could not walk and he was going blind. After a complete medical workup, the doctors told him that nothing could be done for advanced problem.
A diplomat that I knew mentioned to him that I might be able to help him. So, this gentleman and much of his family, bodyguards, and cooks flew down to New Mexico. Many people were surprised to see many Africans in their native costumes driving around Las Cruces in their rented Lincoln town cars. I put him on a diet and exercise program and gave him several supplements including 300 mg of ALA three times a day. In addition, I administered relatively large doses of ALA intravenously to him. In about a month, he started to recover. He was able to walk slowly and his vision started to improve. When he left, he was much improved. I heard, however, that when he returned home, he stopped following the protocol and became ill once more.
Adherence to any medical program is really a problem. Most of our patients get better when they are in town, but when they return home many of them revert back to their old habits that originally caused their medical problems.
Passwater: What is new in ALA research?
Berkson: Recently there has been a lot of cosmetic commercial work with ALA as an anti-aging agent for skin. I always thought if ALA was effective in preventing damage to the liver or kidneys, it could be just as effective as a rejuvenating skin cream. In the 1980’\s I brought this idea to the attention to the president of a large cosmetic company. I was told that he had no interest in ALA and if it was any good he would have heard about it by now.
In the 1960s and 1970s, the Japanese and Germans did some interesting work healing skin lesions with ALA. Much of this work was continued at Dr. Packer’s lab in the 1990s. One paper actually demonstrated that solar radiation damage to skin could be modulated with ALA.
Recently, a group at the University of Mississippi showed that ALA/prescription drug combinations could possibly be effective for treating psoriasis and contact dermatitis. They knew that ALA when applied topically to skin penetrated very easily and was reduced to dihydrolipoic acid. Both forms provide antioxidant protection to the skin.
Others have shown that aging of the skin involves free radical damage leading to cross linking of collagen fibers. This process can easily be seen in the looseness and wrinkling of skin as people grow older. Dr. Thirunavukkarasu and his group from India in 2004 demonstrated that free radical-induced skin abnormalities can be prevented by first administering lipoic acid.
It is interesting to note that ALA has been studied for a long time. It was first discovered as an essential growth factor in bacteria by two U.S. researchers in 1948. In 1951, L.E. Reed from the University of Texas extracted it from calf’s liver and named it alpha lipoic acid. Dr. Reed realized that ALA was fundamentally important as a biological agent that was required for normal aerobic respiration in mammals.
North American scientists have understood the potential importance of ALA as a therapeutic agent for over 50 years now, but because no American corporate sponsor has picked it up for production as a prescription drug, it is still little known by the United States public and medical community, in spite of the fact that it was discovered here. It seems that if a therapeutic agent is not marketed by a big pharmaceutical corporation, it never receives the attention it deserves.
Passwater: Dr. Berkson, once again I thank you for sharing your knowledge and experience with us. We’ll be looking forward to later updates. WF
© 2005 Whole Foods Magazine and Richard A. Passwater, Ph.D.
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