© Whole Foods Magazine March 2002
The Coenzyme Q-10 Breakthrough Part
3: CoQ and Cancer
by Richard A. Passwater, Ph.D
In this issue, we continue our discussion with William V. Judy, Ph.D., to see why mainstream researchers are getting very excited about coenzyme Q-10 (often simply called CoQ or CoQ-10). CoQ research is moving beyond the mere assertion of its bioenergetic and antioxidant activity to a level where it is respected for having major health benefits as a legitimate dietary supplement. Research still centers on CoQ's benefits to the heart, but new frontiers are opening, thanks to recent findings in 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.
This month, we again chat with Dr. Judy, this time focusing on his research with CoQ against prostate cancer. Dr. Judy 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. He also studied with and worked alongside Dr. Karl Folkers, who generally is conceded to be "the father of CoQ."
In future discussions, we will concern ourselves with Dr. Judy's latest research findings involving children born with impaired ability to produce CoQ and then move on to important topics about CoQ as a dietary supplement.
Passwater: Dr. Judy, when we left off, we were chatting extensively about your earlier research and association with Dr. Karl Folkers. Did you or Dr. Folkers have any scientific rationale for the role of CoQ as a cancer therapy agent or as a way to control or prevent cancer?
Judy: I didn't, but Dr. Folkers, who was a peptide chemist, did. In 1994, he published a paper on the potential of CoQ in cancer therapy, and in 1996, he was working on a report on the relevance of the biosynthesis of CoQ and the four nucleotide bases of DNA as a rationale for the molecular causes of cancer. He also was exploring it for use in a therapy. Dr. Folkers was aware of much more than any of us. He asked us to pull out the files of those heart failure patients we treated for years who also had cancers.
So we went back through our files and found about 15 patients who had their cancers disappear or go in remission while they were on CoQ therapy for heart disease. We published this information in the Biochemical and Biophysics Research Communications in 1993.
That study was the prelude to the Lockwood paper. Dr. K Lockwood, a cancer surgeon in Denmark, did breast cancer studies with CoQ as part of a nutritional package given to all cancer patients. This was a requirement of the Danish government.
Passwater: Wow, they are ahead of the United States in this respect. That alone seems like a good story for another day.
Judy: Dr. Lockwood's first study involved 30 patients wherein four or five patients had tumors in their breasts the size of your thumb, and they started to go away. When the dose was increased from 90 mg to about 300 mg a day, the tumors disappeared. The researchers presented this study in 1993 at a Stockholm meeting, but they released it too soon because they didn't have enough data.
Nevertheless, Swedish researchers became interested but they didn't have enough information regarding dosage. Nor did they recognize the long time interval required for CoQ treatments to become effective. They were approaching CoQ as a drug and expected tumor suppression in weeks instead of months. This did not please Dr. Folkers. We had been back and forth to Europe with Dr. Folkers many times lecturing and helping set up clinical protocols in heart failure in Europe, (Sweden, Germany, Switzerland, and Italy). Now he was again doing the same for cancer studies all over Europe.
Dr. Folkers wanted me to work on cancer and gave me the choice of which cancer type to investigate.
Passwater: Why did you choose to work on prostate cancer?
Judy: We had a couple of such patients in our heart failure studies, and it is a major growing concern in the U.S.A We also have a good biochemical marker (PSA) for this cancer and the prostate gland is easy to study anatomically.
Passwater: Tell us about these studies.
Judy: We conducted three small open-labeled studies over three years. There was no conventional therapy being given during the studies. The CoQ dosage was 600 mg/ day given initially in a 90day protocol. Overall, 32 patients with different stages of prostate cancer were studied. All patients had low plasma CoQ levels. The initial study group (N=l5) consisted of advanced cancer patients who had been through hormonal, chemo- and radiation therapies. In 90 days. we saw no changes in PSA, but all the patients were feeling better with improved energy, improved appetites and improved urinary function. Dr. Folkers was disappointed that we did not see the PSAs decrease. I reminded him of how long it was before Dr. Lockwood saw an effect in the breast cancer patients. Since we had the patients. the CoQ, and the patients were happy and wanted to continue, Dr.
Folkers agreed to continue.
In about 120 days, we began to see the PSAs start to go down. In a year, the PSAs dropped 75% in 14 out of 20 volunteers, and the prostate mass was decreased by almost 64%. Prostate biopsies in six patients who would allow this procedure indicated no active cancer cell activity. Dr. Folkers was excited, I was excited, and the patients knew they were improved.
Passwater: What happened next?
Judy: That year Dr. Folkers went to Europe three times to set up other clinical trials and search for additional funding. That got him out of his depression. We ran two more trials. He wanted to see the effect of CoQ in different stages of prostate cancer. He was trying to determine if adding vitamins 8-2, B-6 and 8-12 could shorten the time needed for CoQ to take effect. Fortunately, my wife worked with a group of urologists who managed prostate cancer patients. We gave them 600 mg of CoQ plus the B vitamins. Again, the PSAs and the prostate mass decreased, but the response time was not shortened.
Passwater: The only treatment you gave them was CoQ supplementation?
Judy: Yes, in the initial study. They all had previously had, or refused, conventional therapy. In the second study, with early onset cancers and another advanced group, we added vitamins 8-2, B-6, and 812 to the CoQ supplementation.
Passwater: Why did you add these metabolic vitamins?
Judy: Dr. Folkers believed that these vitamins might metabolically enhance the direct effect of CoQ on the cancer cell. I wasn't sure that CoQ was having a direct effect on these patients' cancer cells because of the long response time.
Passwater: What were the results?
Judy: We reproduced the findings of the first study, but the B vitamins did not reduce the response time in either the second or third study. In our experience, one must be prepared to wait for more than 120 days before one starts seeing the PSA and tumor size go down. Thus, this is not like a direct drug response on the tumor.
Passwater: How long ago was this?
Judy: The year was 1997.
Passwater: Yet few people know about this. Did you follow up with more studies?
Judy: No, I didn't. But Dr. Folkers had set up one study in Sweden with Dr. Marcus Nylander to reproduce our findings. Dr. Folkers made three trips that year. 1997. I was in Los Angeles at a meeting when Dr. Folkers called me and told me he had been funded by a Swedish pharmaceutical company to do more CoQ and prostate cancer studies. He told me he was on his way back to the United States after visiting his granddaughter, a medical student in Stockholm, during our Thanksgiving holiday. He asked me to call him when I returned home. Before I left California at the end of the week, my wife called and informed me that Dr. Folkers returned home, had a delayed Thanksgiving dinner with his daughter and her family, toasted each with a bottle of his favorite white wine and went to bed.
That night he passed away in his sleep.
His daughter told me she knew he was happy because he was again excited, planning more research on his life's passion.
Passwater: Before he left for Europe, he had agreed to do an interview with me when he returned. I was really looking forward to it. Sad as his passing was, the main thing is that this great man died happy and peacefully after a long and productive life. Who could ask for anything more?
Now, Dr. Judy, tell me this: when Dr. Folkers died, did this line of research die with him?
Judy: No, we have continued to stimulate research in this area. Dr. Nylander conducted a clinical study in Sweden. I saw some of the data through 240 days of CoQ therapy. The researchers appeared to be reproducing our findings. In 1998-2000, the Bard Prostate Cancer Clinic in New York conducted a large trial in which 500 to 600 mg/ day CoQ was given along with a total body-cleansing compound. This team also appeared to have reproduced our findings. We have collaborated with dozens of physicians and hundreds of patients who are using CoQ to control prostate cancers.
Passwater: Did you ever receive the funding for additional studies Dr. Folkers secured in Europe?
Judy: No, we waited for calls from the Folkers Foundation for weeks. When I finally called to inquire about the funding, no one knew what I was talking about. Dr. Nylander confirmed the potential funding agreement to Dr. Folkers, but there was no signed agreement. Thus, the funding stayed in Europe.
Passwater: What has happened to the data collected in the studies you have discussed?
Judy: The studies Dr. Folkers and I conducted were "tied up" by the Folkers Foundation until just recently. Since the Folkers Foundation funded the studies, they owned the results. I took Dr. Folkers' place at an ACAM meeting in 1997 to discuss the role of CoQ in the genesis and treatment of cancer. I released some of the data at that meeting. That release created some clinical interest but no large clinical trials until the Bard Clinic study. Our studies, that of Dr. Nylander, and a Danish study were submitted for presentation and publication at the 1998 International Coenzyme Q10 Association meeting in Boston. The organizing committee felt that the release of these studies was somewhat premature. I'm sure that they desired to have more definitive studies presented. At the international meeting last year in Frankfurt, Germany, a couple of basic science studies were presented, in which CoQ was shown to induce cancer cell death in mice with estrogen-sensitive breast cancer. Again, this is exciting, but the mechanism is unclear.
We have consulted with hundreds of patients with different cancers who used CoQ as a complementary bionutrient to prevent many of the adverse side effects associated with conventional chemo- and radiation therapies. These therapies hinder CoQ function and/ or synthesis. These people become CoQ deficient. This is why Dr. Folkers found major CoQ deficiencies in patients with almost all forms of cancer who received radiation or chemotherapy. Keeping the CoQ levels up maintains energy synthesis, boosts the immune system, and promotes tissue repair and healing during radiation therapy. There are less adverse side effects-nausea, vomiting, hair-loss, cardiac arrhythmias -- and in the end, a much more stable, functional and happier patient during and after the conventional therapies. We have experience with hundreds of these patients, not only in prostate cancer, but also in colorectal, pleural, lung, peritoneal, pancreatic, liver, bone and some brain cancers.
Passwater: Did the Folkers Foundation or the University of Texas pick up on these studies?
Judy: Not really. I haven't seen any results from such activities until the recent work by Dr. Richard Willis on CoQ and apoptosis of the estrogen breast cancer cells in rats. Dr. Willis worked with Dr. Folkers at the University of Texas and was a member of the Folkers Foundation Board. The University of Texas has evidently closed the Institute for Biomedical Research that Dr. Folkers headed. The Folkers Foundation that funded our prostate cancer studies appears to have become inactive since his death.
We had a partially written manuscript at the time of Dr. Folkers' passing. This was tied up by the Folkers Foundation until recently. Perhaps, now, we should finish the discussion with new information about possible mechanisms and publish the work. Anyway, that was my last research effort with Dr. Folkers.
Passwater: Did you ever find a copy of the paper Dr. Folkers was writing?
Judy: No. Supposedly, he had sent it to Austin for typing. We weren't able to find the discussion or the other parts of the manuscript I had written-not in his New Hampshire office, nor in his briefcase, nor in Texas. He did show Dr. Nylander a copy when he was in Sweden, but it evidently did not get home with him.
Passwater: Why was Dr. Folkers writing this discussion?
Judy: As the father of CoQ, he was the most appropriate person. He was, as we noted, a peptide chemist and had written an earlier paper on the relevance of the biosynthesis of CoQ and the four bases of DNA as a rationale for the molecular cause of cancer and the possibility of CoQ being useful in cancer therapy (Biochemistry and Biophysics Research Communications, 1996) .
Passwater: Did you or Dr. Folkers have an explanation or theory as to the mechanism involved in CoQ and cancer?
Judy: My thought was that it was not a direct effect of CoQ on the cancer cell since there was such a long response time. I was leaning toward CoQ's enhancement of the body's natural defense through the Natural T Killer cell. Most likely, I believed, we were observing an effect of CoQ on the synthesis of the protein cytotoxin these cells produce and inject into cancer cells that kill the cancer cells. Dr. Folkers had several possible explanations. These ranged from CoQ and protein synthesis control to the oncogenes associated with cancers. It will take the extensive work and combined efforts of the peptide chemist, immunologist, and the oncologist to solve this problem. It is well known that CoQ is a very important component of the immune system.
Passwater: Have any of these data been released?
Judy: Yes, Dr. Folkers had been invited to make a presentation on the possible role of CoQ in cancer therapy and the genesis of cancer at an ACAM meeting in Florida. After his death, the organization asked me if I could take his place. I gave the presentation and included two slides from the prostate cancer study. I didn't have enough data to support Dr. Folkers' theory, but I had a lot of data to support the use of CoQ in cancer patients with CoQ deficiencies of unknown etiology.
Passwater: You indicated that the Folkers Foundation that Dr. Folkers established to fund CoQ research, as well as the Biomedical Research Institute at the University of Texas that he headed, are both inactive. Why?
Judy: The institute at the University of Texas is no longer doing plasma or tissue CoQ analysis for researchers outside the university. Yet, it must be active because the paper presented by Dr. Willis at the International CoQ Association Meeting in Frankfurt, Germany last year carried the institute name. The Folkers Foundation, which funded much of our work and that of others, does not appear to be active. Evidently, the funds which Dr. and Mrs. Folkers earmarked for use after their deaths have not become available to support continued CoQ research in the USA as he desired. In the last year of his life, Dr. Folkers established an award from the Foundation to CoQ researchers who made significant contributions to the cause. Dr. Crane received the first of these at the International Meeting in Italy in 1996. No awards were given at the Boston meeting in 1998, which was a tribute to the lifelong work of Dr. and Mrs. Folkers, nor at the Frankfurt, Germany meeting last year.
Passwater: But you are still conducting CoQ research at the Southeastern Institute of Biomedical Research (SIBR)? That is correct isn't it?
Judy: Indeed. We still are looking for more absorbable CoQ product forms, and thus do many absorption studies for various groups. We continue to work in low- energy syndromes that occur naturally, with age, with diseases, or that are induced by pharmaceuticals that interfere with CoQ synthesis or its essential role in energy synthesis through the mitochondrial electron transport system. We have been active in investigating the influence of CoQ along with other sugar balancing nutraceuticals, in refractory Type I and Type II Diabetics, and in weight management..
Passwater: Your latest research, especially with babies having Prader Willi Syndrome, has attracted the attention of not only biochemists and nutritionists, but also developmental geneticists.
Judy: Being trained in metabolism and bioenergetics as a young scientist, I always have been interested in the relationships between low CoQ synthesis, low metabolic activity and obesity. Several years ago we found a genetic syndrome in babies in which there is a CoQ deficiency.
It appears that these babies cannot make enough CoQ in their skeletal muscles. Thus, they have low muscle tone, weakness, delayed development, mental retardation, food foraging, and become overweight. This is exciting to us in that it involves infants and the first discovery of a CoQ deficiency in newborns. If nothing else, this research should prove to the clinical community the essential role of CoQ to cell energy synthesis function and to the quality of life as described by Dr. Folkers when he received the American Chemical Society's Priestly Medal for his outstanding work in chemistry (1986), and the President's National Medal of Science (1990) .
Very few people know the impressive history of CoQ. It all started in the U.SA with the discovery of CoQ by Dr. Crane. The Nobel Prize was awarded to Sir Peter Mitchell in 1987 for his work in how cells of the body produce the energy to run the life processes, and CoQ has the pivotal role in this process. The outstanding work of Dr. Robert Beyer at Michigan State, which along with the collaborative work of Dr. Lars Ernster in Sweden, paved the way for developing the antioxidant function of CoQ. There is so much to tell about CoQ, but we have limited time before the new leaders will make even more important discoveries relative to the role of CoQ in nutrition, health and disease.
Passwater: It is very exciting research, but let's discuss that the next time we get together. First, tell us a little more about the overall work of SIBR
Judy: SIBR is a five-year-old contract research company that Dr. Folkers helped us start in late 1995. We do clinical research and join hands with the local clinical community for specific patient populations and well-managed patients. We operate a free-standing facility in Bradenton, FL, located on the west coast between Tampa and Sarasota. We conduct clinical research protocols for the nutraceutical and pharmaceutical industries. We opened our doors to the entire U.S., Asian, and European natural products industry last year. Our studies are reviewed and approved by Institutional Review Boards (IRE) for patient safety, and thus registered with the FDA We conduct randomized, double-blind, placebo-controlled protocols in a timely manner and at a reasonable cost compared to that found in the university system. We use outside, certified, clinical laboratories for analytical studies, and statistical support groups. A physician is our medical director, and we have certified clinical research coordinators and research nurses. We can do studies with either small or large numbers of subjects consisting of both normal and clinical volunteers.
We lecture at both domestic and international natural products industry meetings about CoQ and other products. We recently visited four major Indian cities to train 549 cardiologists, cardiac surgeons, internists and diabetologists in how to use CoQ clinically. We have done the same in Italy, Switzerland, Germany, Denmark and Sweden. In these countries, we represented pharmaceutical companies that established CoQ clinical studies.
We believe that regulatory agencies are forcing members of the natural products industry to conduct or fund their own clinical research on natural products. We design clinical protocols or conduct protocols provided to us, provided they are approved by an IRE. Our group has been doing clinical research for a combined 72 years. We all came out of the university research industry. We enjoy what we- do, and we feel that we do it well. As a supportive company for the natural products industry, we realize the importance of research to the future of natural products and nutrition. Hard data are a must if this industry is to make its maximum impact in the field of alternative/ complementary therapies.
Passwater: Well, thanks for discussing the human side of CoQ with us. Next time around, we will chat with you in more detail about these exciting findings uncovered by your most recent research. WF
Worm CoQ Study Attracts Interest
While Drs. Richard Passwater and William V. Judy were still involved in the interview process. a study of CoQ in genetically altered worms was published in the January 4, 2002 issue of Science. This article. which suggested that large intakes of CoQ could shorten the worms. life spans. received wide attention in the media and on the Internet. Both Passwater and Judy have expressed misgivings about this finding and questioned the implications drawn and the theoretical interpretations suggested by the researchers as a possible explanation for what they observed. They also questioned the relevance of the studies to humans and the fact that they suggest excess CoQ can become a pro-oxidant in humans.
While holding out the possibility of covering this study in detail in a future issue of WHOLE FOODS. They nevertheless presented a short version for publication here. On the one hand, both Passwater and Judy declined to take issue with the possibility that there may indeed be an upper limit to the dietary intake of CoQ. As Passwater pointed out, "Of course. everything has an upper limit of optimization of intake-even oxygen and water."
Judy chimed in. "While we may not know the range of optimal dietary intake for CoQ. we do know several facts. We know of Laplander, Eskimo and Asian groups who naturally have plasma CoQ 60% to 80% greater than we find in a typical resident of the United States. These people live well beyond the 1Oth decade, and have no age-related degenerative diseases. heart failure. diabetes. Parkinson's. etc. As for babies, we are increasing their blood levels to 6-8 mcg. of CoQ per ml. After one year we have no sign of enhanced oxidative stress. In fact. their wrinkles disappear.
They are lean, strong and develop normally:
As illustrated in the accompanying interview. Bill Judy has used 400-600 mg of CoQ daily for long periods of time in his anti-cancer clinical studies with outstanding results. In this work, he has found that the amount of CoQ transported from the blood to the cell and used in the mitochondria appears to be limited. Thus, excessive buildup of CoQ does not occur. Judy said that CoQ researchers have been on the lookout for upper limits of safety for their clinical studies. He noted that clinical trials are governed by committees looking out for safety issues. Researchers have even studied CoQ levels within the lymphatic system from the intestines, and lymphatic system-blood system interchanges. "But even after 20 years of tracking CoQ movement within the body," he concluded, "we have no such evidence of CoQ toxicity or CoQ changing from an antioxidant to a pro-oxidant."
Some background may help readers better understand the experiment that was reported in Science. According to Passwater, the Caenorhabditis elegans nematode worms studied by UCLA researchers Pamela Larsen and Catherine Clarke normally produce coenzyme Q-9. which is an isoform of the CoQ that is produced in humans. The worms in the study. however. were altered genetically so as to knock out the gene responsible for coenzyme Q-9 production. Passwater cited earlier studies showing that the addition of coenzyme Q-9 to the diets of these genetically altered worms increased their life spans.
In this study, however. the researchers added a lot more coenzyme Q-9 to the worms' diets, and these very high levels of coenzyme Q-9 shortened the life spans of the worms. Passwater remarked. "Now, we don't know exactly how much CoQ they added, nor how it corresponds from worm to human dosages. But we suspect it was very high indeed. probably exceeding by far any comparable dosage that would be considered for humans. Worms metabolize their diets differently from humans. In the early 1990s. Drs. Bob Beyers (of Michigan State University) and Lars Ernster (a researcher from Sweden) proved that these anomalies do not occur in the mitochondria of rodents and man. This reported phenomenon may be specific to worms only."
In any event. Passwater emphasized. "One thing we can be sure of is that the data from this short experiment over a few weeks with a few hundred worms sheds no information that can be directly extrapolated to humans."
© 2002 Whole Foods Magazine and Richard A. Passwater, Ph.D. This article is copyrighted and may not be re-produced in any form (including electronic) without the written permission of the copyright owners.