Coenzyme Q: New Kind of Immune Modulator?

Published in SAN FRANCISCO SENTINEL, February 27, 1987;Also published in AIDS TREATMENT NEWS, same date.

Coenzyme Q, a naturally occurring substance found in many foods and necessary for life in every cell of the body, is sold in pure form in capsules in most health-food stores. No scientific studies have tested it as a treatment for AIDS or
ARC. But animal studies have shown that coenzyme Q might be a new kind of immune modulator. It may not increase the total number of T-cells. But correcting a deficiency of coenzyme Q, which may develop especially in illness, can make each cell more effective and may restore the balance between different types of T-cells. Coenzyme Q also has other, better known medical uses, and a history of beneficial synergy when used together with certain other treatments.

No toxicity or harmful side effects have ever been reported; safety has not been an issue. This treatment
possibility appears to have no drawbacks or dangers. But since persons with AIDS can respond to treatments in unexpected ways, safety cannot be guaranteed until medical tests have been done. Unfortunately we cannot find any evidence of plans or preparations to test coenzyme Q in the treatment of AIDS or ARC.


What Is Coenzyme Q?

Coenzyme Q, abbreviated "CoQ" (pronounced "co-cue") and also known as ubiquinone, is like a vitamin; many ordinary vitamins in fact work as coenzymes. However, CoQ does not meet the technical definition of the word "vitamin", because the body can produce its own supply in some cases.

Like vitamins, CoQ is essential to life. It plays an essential role in the complex series of biochemical reactions
by which cells perform respiration and release energy. A 25 percent deficiency can cause disease, and a 75 percent
deficiency can cause death. But if there is already enough CoQ, taking more will not help.

Only one form of coenzyme Q, namely coenzyme Q-10, is used in human metabolism, and by most other vertebrates. Other animals and plants may use other forms, such as Q-9, Q-8, etc. The numbers refer to the length of a chemical chain which is part of the molecule.

In the body, the highest concentration of CoQ is found in the heart -- not surprisingly, since CoQ allows cells to
release energy, and cells of the heart must release abundant energy. High concentrations are also found in the liver, and in the cells of the immune system. The heart, and probably also the liver and immune system, are especially vulnerable to CoQ deficiency. The need for CoQ may increase during illness.

The most concentrated "natural" source of CoQ readily available in the American diet is beef heart and other red
meat. Spinach, peanuts, and some other foods also contain significant amounts.

For many years CoQ was a laboratory curiosity, after its discovery in 1957, because of the expense of purifying it from
sources such as beef hearts. But today Japanese companies have learned to produce large amounts cheaply, using micro-organisms in a fermentation process. Japan is the undisputed leader in the development and use of CoQ, and the only country to produce it in quantity.


Medical Uses

In Japan, over ten million people use CoQ as a prescription medicine, usually for the treatment or prevention
of heart disease. Major scientific tests involving a total of thousands of heart patients have found that CoQ helped over 70 percent of them. These people had serious illnesses such as congestive heart failure and angina.

One double-blind heart disease study found "extraordinary clinical improvement" in patients who had been "steadily
worsening and expected to die within two years under conventional therapy" (Langsjoen and others, 1985).

In the U.S., CoQ is not approved as a prescription medicine for any purpose -- although it is sold over the counter in health-food stores. We interviewed Emile Bliznakov, M.D., a leading CoQ researcher and author of the only popular
book on the subject (see reference below). He emphasized that the U.S. Food and Drug Administration is not the problem, and does not oppose efforts to get CoQ approved. Today CoQ is in "phase II" clinical trials, meaning large-scale tests of its effectiveness (not for AIDS or ARC, however). The time required for phase II depends on "money and organization". Since no major pharmaceutical company is pushing for U.S. approval for CoQ, the trials must be done piecemeal, through small-scale tests at universities and research institutes. Fortunately the FDA today will sometimes accept evidence from foreign studies; it used to require these tests to be repeated in the United States.

Since CoQ occurs naturally in foods, U.S. law permits it to be sold over the counter, but only without medical claims.
Most doctors don't use unapproved treatments, however, so few of the patients who could benefit from CoQ have heard about it. We have a confusing situation of a completely safe, probably lifesaving medicine which patients can find out about and use on their own, but usually not through their doctors.

CoQ has also shown dramatic results in treating periodontal (gum) diseases. It has been used in cancer
treatment, mainly to reduce heart damage caused by the anti-cancer medicine adriamycin. It shows promise for reducing high blood pressure, and for helping some people lose weight. Researchers are testing CoQ as a treatment for several other diseases, including muscular dystrophy and allergies or asthma, but its effectiveness is unknown.

Some people are using CoQ in the hope that it could extend the human lifespan. Obviously no human proof is available, but an animal study found that CoQ extended the lifespan of mice up to 50 percent. The treated animals remained youthful looking during that time. CoQ becomes deficient in aging animals, and supplying it can correct much of the immune deficiency which develops in aging. CoQ is also a strong antioxidant, like vitamin E, and believed to be highly effective in neutralizing free radicals.

Dr. Karl Folkers, one of the world's leading researchers on CoQ, has proposed the term "diseases of bioenergetics" for conditions which result from lack of sufficient energy release in the metabolism of cells.


Immune Effects

Unfortunately most of the research on immune effects of CoQ stopped around 1981. What we do know from the several animal studies which had been done by then suggests that this treatment deserves another look.

A 1981 paper by Dr. Bliznakov (see reference below) reviewed some of these studies, and stated several conclusions: * A number of different measurements, including resistance to viral and parasitic infections, showed that CoQ was an immune modulator; it was especially effective when given with other drugs.
* Animals could develop deficiencies of CoQ during illness, and/or during aging.
* The effects appeared to be due to increased activity of existing cells, not an increase in the number of cells.
* Dose can be important. No toxic effects have ever been found, even at high doses. But certain other immune modulators can become ineffective or even counterproductive if very large amounts are used, and CoQ might behave similarly.
* Since no harmful side effects were known, CoQ should be tried "for clinical application in disease states in which the
immune system is not operating on an optimal level".

Six years later, in January 1987, Dr. Bliznakov published his popular book on CoQ. Millions of people have used CoQ in Japan with no harmful effects. The new book has a chapter on AIDS; it describes animal studies showing that the level of CoQ in the thymus declines with age, and that CoQ given to elderly animals restored immune response associated with the thymus to almost youthful levels.

In our telephone interview, Dr. Bliznakov explained that in animals CoQ has significantly prevented or corrected several different kinds of immune deficiencies -- caused by three different immunosuppressive chemicals (adriamycin,
cyclophosphamide, and hydrocortisone acetate), by aging, and by a virus. The inference is that it might also help prevent or correct immune deficiencies caused by ARC or AIDS.

In a completely separate study, Dr. Karl Folkers found that CoQ could increase the level of antibodies in the blood of
humans (Folkers and others, 1982). This effect might be either helpful or harmful to persons with AIDS. It took a long time -- 35 to 132 days depending on the patient -- for an observable increase to occur.

CoQ has been largely ignored in the United States, and so far this writer has talked to only one person with AIDS who has been using it (we have heard of others). The person I talked to could not comment on effects he experienced, because he was also trying so many other experimental treatments that he could not tell which ones were responsible for which results. It is notable that this person, during the one evening we met, had so much energy that he would have stood out even among those who do not have AIDS and are completely healthy.


This Writer's Experience

As part of the research for this article, I tried CoQ, and have been using it for twelve days as of this writing. Having
heard that it could take three weeks or more to notice results, I decided to try a moderately large amount for one month, and then if there were any beneficial effects, find a smaller dose which would maintain them. I tried 60 mg per day of the
Twinlab CoQ10 (tm) product, two 10 mg capsules with each meal. The 60 mg dose is twice the maximum recommended on the bottle, but about in the middle of the range of therapeutic doses commonly used in medical studies (30-100 mg per day). The cost, incidentally, was a little over one dollar a day; careful shopping could reduce it greatly.

The main result has been feeling far less fatigue during the daytime, and needing less sleep. I have felt more energy
than I've felt for several years, and have been able to do at least an hour's additional productive work each day. Other
effects have included being less sensitive to cold and finding that cuts heal faster.

Subjective results can easily reflect a placebo effect. In this case, however, all of these outcomes were unexpected.

I first noticed results after only three hours, and have heard that people trying CoQ as a food supplement often feel
effects quickly, within a day or two. However, the medical studies usually find that it takes three weeks or longer to
obtain benefits. This discrepancy may reflect the fact that the medical patients were very ill, often with life-threatening
conditions. And medical studies usually look for physical, measurable results, rather than subjective reports on how
people feel.


The Future

Apparently no one plans to do any scientific test of CoQ for treatment of AIDS or ARC. And even if researchers started now, it would be years before the studies were designed, funded, conducted, analyzed, published, and accepted -- in addition to the time required to get government approval. In short, it will take years for U.S. medicine to get CoQ to persons with AIDS or ARC, even if everything goes right and happens as fast as possible.

The lack of testing raises public policy questions about the management of AIDS research. The case for trying this
treatment was almost as strong six years ago when AIDS was first recognized as it is today -- through information
available on the shelves of any large medical library. In these six years nothing has been done concerning CoQ and AIDS. Apparently it wasn't anybody's job to search out promising scientific leads and make sure they were followed up.

Meanwhile, most health-food stores sell CoQ over the counter. Millions of people have used it in Japan as a
prescription medicine, without any toxicity or harmful effects. This food supplement is inexpensive and easy to use. Clearly people will try it and see if it works for them, with information spreading by word of mouth, grass-roots
organizations, and informal publication. Some physicians are willing to try promising treatments without waiting for
official approval, or at least monitor their patients' use of them. Hopefully these physicians will help to collect
information systematically and let their patients know of any news which develops.

No one expects CoQ to cure AIDS or ARC. The question is whether it can be helpful as part of an overall treatment
program -- for some people at least. Until tests are done we cannot be sure. The information available does suggest that CoQ is a plausible treatment possibility which deserves attention.


For More Information

The only popular book is The Miracle Nutrient Coenzyme Q-10, by Emile G. Bliznakov, M.D. and Gerald L. Hunt, published by Bantam Books, January 1987. This book includes over a hundred references to medical and scientific papers. Dr. Bliznakov is one of the leading researchers on CoQ and the immune system and is also president and scientific director of the Lupus Research Institute.

Omni magazine has a one-page article about CoQ (February 1987, page 24).

Hundreds of technical papers have been published. A major recent book is Coenzyme Q: Biochemistry, Bioenergetics and Clinical Applications of Ubiquinone, edited by G. Lenaz (John Wiley & Sons, 1985). Four international symposia have been held, in 1976, 1979, 1981, and 1983, and the proceedings have been published.

Other papers referred to above are:

Bliznakov EG. Coenzyme Q, the immune system, and aging. In Biomedical and Clinical Aspects of Coenzyme Q, Volume 3, pages 311-321. Elsevier/North-Holland Press, 1981.

Folkers K, Shizukuishi S, Takemura K and others. Increase in levels of IgG in serum of patients treated with coenzyme Q- 10. Research Communications in Chemical Pathology and Pharmacology, Volume 38 number 2, November 1982.

Langsjoen PH, Vadhanavikit S, and Folkers K. Response of patients in classes III and IV of cardiomyopathy to therapy in a blind and crossover trial with coenzyme Q-10. Proceedings of the National Academy of Sciences USA, Volume 82 number 12, pages 4240-4244, June 1985.