© Whole Foods Magazine
The Coenzyme Q-10 Breakthrough
Part 1: The Untold Story
Richard A. Passwater, Ph.D.
Why are mainstream researchers getting very excited about coenzyme Q-10 (also known as CoQ or CoQ10)? What has changed their viewpoint from that of CoQ being merely an obscure nutrient having both bioenergetic and antioxidant activity to that of one promising major health benefits as a legitimate dietary supplement? It seems that this excitement is due to a combination of the latest findings in heart disease, low-energy syndromes, cancer prevention and treatment, new discoveries in neuro-degenerative diseases, stabilization of the nucleotides in protein synthesis, and low-energy syndromes and poor physical and mental development in genetic syndromes.
It doesn't seem possible that it has been 15 years since April 1987, when this column predicted CoQ would become "The Nutrient of the 90's." Of course, I have often discussed CoQ since then, but I haven't devoted an entire column to CoQ since 1987. However, that is about to change because CoQ is about to break through into the mainstream of the medical profession shortly. Yes, CoQ did become an important nutrient in the health food community in the 1990s-in spite of the repressive efforts of some pharmaceutical companies.
The CoQ story is replete with research efforts denied, doors shut, studies sabotaged, publications refused and jobs lost. Joyously, we are now at a point when the lid of repression is about to be blo\\l1 off. The reasons for the new excitement are both scientific and political. From science comes new research that is about to be released in several areas. From the worlds of marketing and politics comes an expectation that pharmaceutical companies are about to widely disseminate advisories that CoQ should be taken along with the most popular type of cholesterol-lowering drugs, the "statins."
A major pharmaceutical company may soon target both the medical profession and the general public with an educational campaign about the important health benefits of CoQ. Why? Because this company, like others, now realizes the importance of combining CoQ with its cholesterol-lowering drug. This is ironic because some pharmaceutical companies appear to have been involved years ago in repressing reports of the success of CoQ over their cardiac medications. Others had the complete control of CoQ in the world by owning production patents by which CoQ could be manufactured for commercial use.
I have repeatedly warned of this in this column over the years. The statins, which include atorvastatin (Lipitor), simvastatin (Zocor), pravastatin (Pravachol), cerivastatin (Baychol), fluvastatin (Lescol) and lovastatin (Mevacor), work by interfering with an enzyme involved in the natural production of cholesterol in the body. A major problem is that these drugs also decrease the body's production of CoQ, which requires the same enzyme (called HMG-CoA reductase) for its production. The reduction of CoQ is very detrimental and can result in serious health problems. Now, however, a pharmaceutical company has combined CoQ with its drug and is gearing up to educate everyone as to why this fact makes its drug better than its competitors'.
Over the next several months-but not necessarily in consecutive columns-we will chat with CoQ experts not only about CoQ function and its dramatic health benefits, but also about the human side of CoQ research. In this regard, we will discuss how the studies have been repressed, and we will learn about extremely important new research breakthroughs.
In The Beginning
Many readers familiar with CoQ know that Dr. Fred Crane discovered CoQ as a critical compound in the body's production of energy in 1957. Nevertheless, it was Dr. Karl Folkers who ultimately earned the sobriquet, "the father of CoQ" because of his extensive clinical research with CoQ. For decades, anyone thinking of CoQ clinical research would think primarily of Dr. Folkers.
Nor was his work with CoQ his only contribution to nutritional science. At a memorial service, held in December, 1997, the president of the University of Texas at Austin, Dr. Larry Faulkner, said, "Dr. Folkers will be remembered for his many major contributions and assistance to many researchers over a period of more than six decades of research, especially on the structure, synthesis, and medical use of naturally occurring, biologically active compounds, such as alkaloids, antibiotics, B-vitamins, hormones and coenzymes. His unique roles in structural determination and synthesis of B-vitamins, and the isolation and chemical nature of vitamin B-12, provided major advances toward making B-vitamins available for nutritional supplementation."
Among other accomplishments, Dr. Faulkner noted, Dr. Folkers and his group completed the final structural determination and provided the first synthesis of vitamin B-6, performed the first total synthesis of pantothenic acid and was deeply involved in structural .studies of penicillin and (the B-complex member) biotin, eventually providing "an elegant first synthesis of biotin."
Dr. Faulkner continued, "In 1958, Dr. Folkers and his group confirmed the structure of CoQ proposed by Dr. Fred Crane and his group at the University of Wisconsin, demonstrated that CoQ from beef and human were identical, and synthesized Coenzyme Q-9 (which is close to CoQ in structure, but not used in energy production by humans)." Dr. Faulkner pointed out that Folkers, who always believed CoQ should be renamed vitamin Q, adopted this coenzyme as the major research focus for the remainder of his life. At Merck, Sharpe and Dohm, where he worked for some years, Dr. Folkers continued his research on the biosynthesis of CoQ and its role in the genetic dystrophy in mice.
"In 1968," Dr. Faulkner recalled, "Dr. Folkers accepted an appointment as professor of chemistry and pharmacy at the University of Texas at Austin, and as director of his newly-established Institute for Biomedical Research, his research for medical uses of CoQ resulted in the observation that inadequate biosynthesis occurs in tissues of patients with many different disorders and can result from deficiencies of certain nutrients. Working with many collaborators, he helped to demonstrate that benefits result from CoQ administered to patients with muscular dystrophy, periodontal disease, high blood pressure and cardiomyopathy, with life-extending effects in advanced stages. Potential benefits were observed in cancer patients"
Why pay so much attention to Dr. Folkers in an article that is going to feature someone else altogether-Dr. William Judy. The simple answer is that it is important to establish that Dr. Folkers and his research are well-known in the academic research community and that Dr. Folkers was one of the most respected and highly acclaimed scientists of the 20th century. He, along with his colleagues, including Dr. Bill Judy who is interviewed herein, published more than 700 reports in the scientific and medical literature. His many prestigious awards are too numerous to include in the body of this article, but they are listed in a separate box.
There is another important point to be made here: the exciting health benefits of CoQ that we are about to discuss in upcoming columns represent the highest caliber of scientific research, but the medical profession has not yet embraced them. I believe that the main reason for this neglect is that the pharmaceutical companies, which supply the medical profession with so much of its "medicinal" knowledge, until now have deemed it detrimental for them to acknowledge the value of CoQ. As a result, when lay people ask physicians about CoQ, they usually are told it is "nonsense."
As I mentioned in the previous series of interviews with Wayne Martin, my early interest in CoQ stemmed from my observation that selenium increased the body's production of CoQ. Dr. Folkers and I were interested in helping people fight certain diseases such as muscular dystrophy by increasing their bodies' CoQ production. You have to remember that in those days CoQ supplementation was not a viable option.
Since the passing of Dr. Folkers at 91 years of age (September 1,1906 to December 9, 1997), the clinical leadership has been assumed by Dr. Gian Polo Littarru (in Italy) and Dr. Bill Judy (here in the United States). They are joined by more than 400 other investigators around the world who were students of the founders of this scientific arena. Prominent cardiologists such as Drs. Per Langsjoen, Peter Langsjoen, Svend Mortenson and Stephen Sinatra are also well-known for their pioneering efforts to bring CoQ into the mainstream of cardiology. In this series, we'll first chat with Dr. Bill Judy about his early research efforts with Dr. Folkers and how the pharmaceutical establishment strove to squelch any news about their discoveries.
In later installments, we'll again visit with Dr. Judy to explore his exciting preliminary research suggesting that CoQ is very effective against some major forms of cancer. We'll also talk about his and Dr. Folkers' research on heart disease. We will then move on and look at his most recent discoveries, which affirm a central role for CoQ in the battle against a wide variety of diseases.
William V. Judy, Ph.D., is the president of the Southeastern Institute for Biomedical Research, Inc. in Bradenton, FL, a clinical research support center for the pharmaceutical and natural products industries. Dr. Judy has 25 years of experience in the basic and clinical sciences relative to CoQ, and has authored multiple basic science and clinical publications. He also has served as contributing author to five medical textbooks and seven reviews on CoQ
Passwater: Dr. Judy, if I remember correctly, you were recruited out of the space program to help Dr. Folkers do his heart research with CoQ. What is the story behind that?
Judy: Not exactly out of the space program but soon thereafter. I had been working with the National Aeronautical and Space Administration (NASA) in the early 1960s. I was a classically trained physiologist with some biochemical training. Most of my training was directed toward biophysics and mathematics of physiology. I did my master's degree work in the bioenergetics of metabolism and temperature regulation.
I started out early in the study of energetics and temperature regulation at the University of Kentucky with the late Dr. Loren Carlson. He was on the space advisory committee and after I finished my master's, I wound up in NASA working on some of the environmental problems of space flight.
Passwater: Interesting. In 1963, I was helping NASA produce ultra-pure, liquid hydrogen to fuel the Centaur, the first liquid hydrogen fueled rocket and the forerunner to the Atlas. NASA "borrowed" me from Allied Chemical Corporation, and I found myself working in the Florida Everglades.
Please refresh my memory, what did your NASA research have to do with Dr. Karl Folkers and CoQ?
Judy: Nothing. At NASA I worked with a cardiovascular physiologist, Dr. George Armstrong. We were involved in measuring cardiac function in space flight. Dr. Armstrong taught me biodynamics of the heart and what we called in those days Guytonian mechanics after a leading cardiac physiologist, Dr. Arthur Guyton, at the University of Mississippi. After the tragic Apollo fire, in which I lost good friends, my research efforts at NASA were severely reduced. So I went back to graduate school. I received a National Institutes of Health (NIH) fellowship to study at Baylor University in Houston.
While there, I studied classical physiology, modern bioengineering, more biophysics and mathematics under Drs. Lee Baker and Lester Geddes. I later went to West Virginia University to finish my doctorate. Meanwhile, Dr. Baker went to the University of Texas at Austin, where he was named chairman of the Department of Bioengineering. That was where he met Dr. Folkers. They had lunch together every day, and they were looking for somebody who had the technical skill to measure cardiac function in heart failure patients without placing catheters in them. Dr. Baker recommended me for a research program at Indiana University because of my involvement with the noninvasive bioimpedance method.
Passwater: Then it was your expertise in the bioimpedance procedures that directed Dr. Folkers to you at Indiana University Medical School where you were a young professor of physiology and biophysics.
Judy: Yes. While I was at Indiana, Dr. Folkers came to see me to discuss CoQ. I was already familiar with it because Dr. Gibson, head of our Chemistry Department, was at the Enzyme Research Center in Wisconsin when CoQ was discovered by Dr. Crane. Dr. Gibson had been doing mitochondria biochemistry for years with CoQ and I was aware of CoQ in mitochondria energy synthesis through the biochemistry seminars.
Passwater: So, that's how you got together with Dr. Folkers. Seems like destiny, although the path was a little circuitous.
Judy: When Dr. Folkers came to me in 1973, he asked me to use my technology to measure heart function in congestive heart failure patients with CoQ deficiencies during CoQ therapy. He wanted to know what happened to their heart function when you gave them CoQ. It took me 10 years to get that study approved by a human research committee. Indiana University never did approve my request.
If you wanted to study a product that wasn't mainstream pharmacology or that was not sponsored by a major drug company, it was all but impossible to do so. This was especially true for a natural product about which little was known in the clinical community. I was advised that if it was my desire to continue studies in the non-invasive bioimpedance technology and CoQ in heart failure, I should take my desires to another institution where there were fewer political pressures from the pharmaceutical industry. This I did, and with the help of a couple of excellent cardiologists who understood cardiac bioenergetics, I got a protocol approved at Methodist Hospital in Indianapolis. These physicians knew the role of CoQ in heart energetics because both had sons who had taken biochemistry classes taught by Dr. Gibson at Indiana University Even so, it took us two years to get the protocol approved at that hospital. It was an open-labeled protocol, and patients were the worst possible candidates, endstage Class IV congestive heart failure patients. They all had significantly reduced plasma CoQ levels.
Passwater: For our readers who may not be clinical researchers, let me explain the term "open label." Simply, it refers to a clinical trial in which no placebo (dummy pill or inert pill) is used and in which both the researchers and the patients know the patients are getting the nutrient or drug that is being studied.
Judy: We enrolled 50 heart failure patients who were the worst cases they could find.
We gave them CoQ (100 mg) in an open label supplemental to their conventional therapy and it turned them around almost overnight.
Passwater: Almost overnight!
Judy: Well, in a few days to a couple of weeks. The cardiologists didn't believe the results. In fact, after a year, by which time 80% of these patients in the open-label study were doing well and classified as Class II CHF patients, the cardiologists made us back up and do a randomized, placebo-controlled, double-blind, crossover study.
Passwater: This type of study is considered the gold standard of clinical research, and the results are taken very seriously. There is no higher level of clinical evidence. "Randomized" means that patients are assigned to either the control group or the experimental group at random. "Placebo-controlled" means that the participants receive either the agent being tested, in this case CoQ, or an inert look-a-like pill called a placebo. This is to negate any so-called "placebo effect" that often occurs due to the mere act of taking a pill that a person believes will be of help. "Double-blind" means that the pills are coded by pharmacists outside of the study, and neither the patients nor the physicians know which patients are receiving which pills until after the code is broken at the end of the study. "Crossover" means that at some point in the study, the group formerly receiving placebos then gets the active agent being studied, and the group formerly receiving the active agent now gets the placebos. Still, no one in the study knows which is which.
Judy: This was a year-long study with 50 different patients. The result was that there were 25 patients either doing poorly or who were stable on classical drugs, while there were 25 patients who were improving. The doctors got so upset because they didn't know which of their patients was on what. We finished the protocol and found out those people who had gotten CoQ had improvement in cardiac function when their CoQ blood levels increased. Those people who didn't get CoQ were somewhat stabilized on normal medicines, but their heart function did not improve. In fact, some deteriorated with time. When the crossover tune came, those patients removed from CoQ experienced a clinical relapse while those who received the CoQ for the first time began to improve. These two studies were my introduction to clinical CoQ research.
Passwater: When were these studies completed, and how long did they run?
Judy: In the first study at Methodist Hospital, we submitted the protocols in 1981, received approval in 1982, and got under way in 1983. The second study got under way in 1984 and ran for one year. When the patients in both studies were taken off the CoQ both experienced clinical relapse and were again given CoQ supplements in addition to their conventional drugs and again clinically improved.
At the same time, we were conducting the initial studies in Indianapolis, Dr. Folkers and Dr. Per Langsjoen of the Scott~1lite Clinic in Temple, TX, as well as Dr. Svend Mortenson in Denmark, were conducting similar studies in heart failure patients. Our results were almost identical.
Passwater: Did you publish the results?
Judy: Yes, but the American journals rejected our papers. So we published in European journals and in a series of books on the biomedical and clinical aspects of CoQ, which was edited by Dr. Folkers. Dr.
Langsjoen did get a publication in the American Journal of Cardiology in 1992.
Passwater: Did you have the same kinds of problems getting American journals to publish your other --non-CoQ-- studies on high blood pressure, heart dynamics and the control of blood flow?
Judy: No. Those research articles were published in magazines specializing in hypertension and circulation research, as well as in other U.S.-based publications.
Passwater: Very interesting! We'll discuss these results next month along with your other research. What concerns me here is that in 1983 you had exciting news about how a simple nutrient, CoQ, could save the lives of very ill heart patients, and yet, today, 18 years later, few cardiologists know about your studies or even about CoQ.
Judy: Dr. Folkers was a chemist with Merck for over 30 years. In all that time, he couldn't convince the company to consider supporting CoQ studies for clinical low-energy syndromes and heart failure. Finally, in the 1960s he took CoQ to Dr. Yuichi Yamamura in Japan. Dr. Yamamura treated heart failure patients with CoQ and got them out of failure. The Japanese did a decade of clinical CoQ studies in the 1960s and 1970s. Dr. Yamamura was so successful he convinced the Japanese company Nisshin Flower and Milling Co. to pursue the production of CoQ in Japan. The firm purchased a partial synthesis production patent from Merck. After years of research, the Japanese Food and Drug Administration (FDA) approved CoQ as a pharmaceutical for the treatment of heart failure. In the 1970s another Japanese company bought a second patent from Merck for making a crystalline form of CoQ through a fermentation process.
Passwater: At that time, was Merck making CoQ in the United States?
Judy: No. Dr. Folkers was making small quantities in his lab for research. He was probably making it by partial synthesis or by extracting it from animal protein, probably fish caught off the coast of Galveston, TX.
Passwater: You mentioned that the Japanese had approved CoQ as a pharmaceutical. Were they also marketing it as a nutritional supplement?
Judy: No. After being sold for almost 20 years as a controlled drug in Japan, CoQ has just this past year become available to the Japanese people as a nutritional supplement.
Passwater: I have read that up to 16 million Japanese citizens are taking CoQ as a controlled substance for heart conditions these days. Does the Japanese medical profession now advocate CoQ as a dietary supplement?
Judy: No, not really. In the early years of its use as a drug for the treatment of heart failure, it was the number three leading pharmaceutical in that nation. Japanese physicians found that the use of CoQ permitted them to use lower dosages of other heart drugs, which meant fewer and less adverse side affects and a better, more stable long-term patient stability and quality of life.
Passwater: OK, sorry to get ahead of the story. You were saying that Dr. Folkers brought representatives of the Japanese pharmaceutical industry to the United States.
Judy: Yes. After our success in the heart failure studies in Indianapolis and Texas, as well as in a lung cancer study in which we prevented the cardiotoxicity of adriamycin with CoQ we felt that we needed to get the American pharmaceutical companies involved. We invited all of those in the Midwest and a few others to a symposium that we organized on CoQ and heart failure. We attempted to get these American companies to join hands with the Japanese companies to fund multi-center clinical trials in the United States.
One Japanese company was willing, but others weren't. Only one American company was willing, so it never happened. Since CoQ was a natural substance produced in the body, it couldn't be patented, and many drug companies felt threatened by it. In late 1985 or early 1986, I was informed that I would not be allowed to do any more CoQ research at Methodist Hospital.
Passwater: I don't need to ask why.
Judy: No one ever told me why, but we had so many doctors using it and so much success. It was the buzz of the whole local research community. I imagine it was pressure from a drug company. Methodist Hospital invited me to stay there and still do research, but not CoQ research. I started looking for a place to go and St. Vincent's Hospital in Indianapolis offered to provide the same noninvasive cardiology clinical service I had set up at Methodist Hospital. The administration recognized that this would save the hospital money. They said that they would be happy for me to do research. but I couldn't do CoQ research. This may not seem much better research-wise, but at least it included a salary and allowed me to further develop my bioimpedance technology
Passwater: But, you did do CoQ research there.
Judy: Not initially- I was doing other types of research with catheters, cardiac devices and other cardiac drug studies. In my second year there I was called to the president's office and told that somebody had donated funds for me to continue the CoQ heart failure research, This was a very large sum of money, but they wouldn't tell me who was behind my good fortune- It was the largest such donation the hospital had ever received. so they couldn't readily say no.
Passwater: Did you ever learn who provided these funds?
Judy: Yes, the gift was from a patient in the initial Methodist Hospital CoQ-heart failure program- This was a very influential person in the Indianapolis financial community. who, at the age of 72 was in severe (Class IV, end stage) heart failure, was hospitalized for the third time in a year, and was given only 30-60 days to live. The presiding physician was part of a protocol using CoQ in heart failure. He offered this patient the opportunity to participate in the study.
Within 10 days of starting CoQ therapy, this person was out of the coronary care unit, home and doing well.
The patient remained on CoQ for 17 years with no heart failure, was able to travel all over the world, remained active in the community, and died at the age of 90 of natural causes, He at one time or another, over a period of 40 years, had affiliations with the boards at Methodist Hospital, St. Vincent's Hospital and Eli Lilly Pharmaceutical Company.
The real frosting on the cake was that when I left St. Vincent's Hospital, there was still 8150,000 remaining in this grant fund. St. Vincent's Hospital would not agree to let me take it with me to Florida to continue the work.
Well, let's go back to when I first learned of the grant I was really excited about the opportunity to do CoQ research on heart disease again. With this kind of funding I got all the support I needed, and the Internal Review Board approved the study. I cranked up the largest study ever done at that time in the world. We enrolled 200 patients in the program over two years. It was a five-year study and a randomized, double-blind study. One hundred patients were given conventional therapy and another hundred were given CoQ plus conventional therapy. It turned out that the patients given CoQ plus conventional therapy did much better than those given conventional therapy alone, The patients receiving CoQ had better survival rates over five years and had better cardiac function as measured by various objective parameters. Today, after more than 20 years, many of these heart failure patients still take CoQ every day and have no major heart failure.
Passwater: And still CoQ goes unnoticed by most cardiologists- We'll discuss this study in more detail in our next installment But, for now, tell us how you expanded on your CoQ research?
Judy: I also became interested in myocardial (heart tissue) preservation during heart surgery, so we started measuring CoQ levels in people before and after coronary bypass surgery. We found that those people who had difficult times with bypass surgery not only had low CoQ levels, but their CoQ levels dropped even lower when they came off the bypass pump- I thought it was a dilution problem relative to getting fluid from the heart-lung machine- It was, however, a true CoQ deficiency in the blood and heart muscle- Thus, the hearts in these patients didn't work well after the surgery.
So we started pre-treating high-risk patients with CoQ before they went to bypass surgery- We found out that when we gave patients with low plasma CoQ levels supplemental CoQ, they went through surgery with good myocardial preservation, no reperfusion injury (tissue damage caused when blood flow is restored)- We were funded by an Italian drug company to conduct the study- We published these findings, but again in Europe At St. Vincent's Hospital, we also studied CoQ and ischemic (reduced blood flow) heart disease, especially in patients with severe ischemic conditions and heart failure who were going to the heart catheterization lab and having reperfusion injury after angioplasty.
Passwater: Did you do other CoQ research there in addition to your heart disease research?
Judy: Yes. We also started doing chronic fatigue and sports medicine studies. We are still involved in these efforts- This takes us up to about 10 years ago- We did a lot of research there with CoQ in the 1980s and 1990s, This provided a foundation for our later research, including the cancer and low-energy syndrome research
Passwater: That sounds both ambitious and impressive, and I'm sure our readers will find it interesting to learn about these more recent research efforts. Let's take a break here, however, and save some of this for future installments- Thank you for setting the scene for what promises to be the story of a thrilling adventure in nutritional health- WF
© 2002 Whole Foods Magazine and Richard A. Passwater, Ph.D.
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