Alcohol, AIDS and Nutrition: An Interview with Dr. Ronald Watson
by Richard A. Passwater, Ph.D.
During last month's chat with Dr. Luc Montagnier, I mentioned the research of Dr. Ronald Watson that indicates that at least some antioxidant nutrients improve important components of the immune system. This was of particular interest to Dr. Montagnier so I described the preliminary research of Dr. Watson's group at the University of Arizona, which he had just reported at the Second International Pycnogenol Symposium held in Biarritz, France in May, 1995.
Dr. Watson and I shared the platform as two of the presenters at that symposium. I had described the dramatic results achieved by Pycnogenol(R) in treating Attention Deficit Disorder, and Dr. Watson reported on Pycnogenol(R) and the immunomodulation in retrovirus-infected mice. The Human Immune Deficiency Virus (HIV) that causes Acquired Immune Deficiency Disease (AIDS) is a retrovirus. Dr. Watson studies in laboratory animal model that is reasonably close to human HIV and AIDS. This model system involves a similar retrovirus called LP-BM5 murine leukemia which produces total dysfuntion of the immune system resulting in murine AIDS.
Many readers may be familiar with Dr. Watson's research with vitamin E and beta-carotene which strongly suggests that they may delay progression of HIV infection to clinical AIDS. Dr. Watson spoke at July's NNFA Convention in Las Vegas on "Nutrition as an adjunct to AIDS therapy."
Dr. Watson has edited 35 books and more than 350 research reports on alcohol, nutrition and their interactions with immunology and cancer. His most recent book is "Nutrition and AIDS" (CRC Press, Boca Raton, FL., 1994) His research focuses on antioxidants to prevent cancer and AIDS by immune enhancement, and the use of vitamin supplementation to treat immunosenescence. He is a professor of research in the Department of Family and Community Medicine of the University of Arizona in Tucson. He has directed a National Institutes of Health funded Alcohol Research Center focusing on alcohol-immunology-AIDS interactions. Dr. Watson received his Ph. D. from Michigan State University in 1971, and studied immunology as a post-doctoral fellow at Harvard University.
As we were returning from Biarritz, we stopped in Bordeaux, the heart of France's best wine country. Over breakfast, we had a chance to chat about recent epidemiological studies on health and wine consumption. I think that many readers will be interested in Dr. Watson's comments on alcohol's negative effects on the immune system. However, first I want to get back to the subject of the effect of antioxidant nutrients on delaying AIDS.
Passwater: AIDS patients exhibit nutritional deficiencies which themselves impair the immune system. HIV infection and poor nutritional status seem entwined -- one as a cofactor for the other. A lifestyle that fosters poor nutrition increases susceptibility to HIV infection, and HIV infection leads to poor nutritional status. Has your research helped identify the individual effects of each factor?
Watson: In some cases, such as drug or alcohol abusers, their lifestyle results in both poor diets and decreased efficiency of absorption of nutrients through the intestine. Adequate nourishment is critical for HIV-positive persons. Several features of HIV infection increase the risk of malnutrition. The gut is a major target for symptoms of AIDS-related diseases, including diarrhea, dysphagia (difficulty in swallowing), oral and esophageal candidiasis, and odynophagia (pain while swallowing). In turn, these complications predispose these patients to malabsorption and sepsis, which furthers malnutrition.
Undernourished persons have impaired immune responses. Particularly impaired cell-mediated immunity, but also impairment in the complement system, phagocytes, mucosal secretory antibody response, and antibody affinity. These immune system abnormalities in turn increase the risk of infection.
It is useful to correct malnutrition, but it may be even more important to learn if specific nutrients can restore the immune system to normal in HIV-infected persons. Thus, our work with a mouse model of AIDS, which is infected with a retrovirus which induces immune dysfunction, is very helpful. We can eliminate the lifestyle factor. The mice consume normal amounts of an adequate diet and do not use drugs or alcohol. Yet, they have higher oxidative damage and lower vitamin E levels. In addition, their immune systems are stimulated by supplemental vitamin E. Thus, it is likely that changes induced by the retrovirus infection induce deficiencies of antioxidant vitamins per se, without any dietary problems.
An important observation is that if the mice consume alcohol or administered cocaine during their retrovirus disease then their immune systems and vitamin E levels are further reduced, with accelerated growth of cancers. Our animals tell us that vitamin E supplementation is helpful, but not a cure, and that even uninfected animals benefit from high vitamin E and other antioxidant intakes.
Passwater: Does HIV infection increase oxidative damage which in turn consumes antioxidant nutrients?
Watson: While the mouse data say yes, the human studies are limited. It does seem likely, but much more needs to be done in this area.
Passwater: Does improving nutritional status in people with HIV-infection or AIDS increase their well-being or longevity?
Watson: This study has not been done in people. In mice, improving nutritional status with supplements of vitamin E increased immune responses during their decline to murine AIDS, but did not extend the longevity of the mice. As death from AIDS occurs due to poor responses to opportunistic pathogens, improving damaged immune systems with nutritional supplements should delay final declines and extend quality and length of life, but the human tests have not been done. Several small studies with beta-carotene suggest improved immune responses, but these studies were too small in scale to show survival benefits.
Passwater: When and why did you become interested in nutrition and AIDS?
Watson: My research has been focused by funding provided by a private non-profit foundation (WGF) for a number of years on the benefits of supplementation with single and then multiple antioxidants in older people whose immune systems are dysfunctioning, but not as drastically as AIDS patients. It became clear that there were significant benefits, especially for the person with a damaged immune system, to multiple antioxidant supplements based upon a surrogate marker like immune responses rather than adequate growth of young animals. So when I got an NIH grant to study alcohol and immunology, it was logical to use a mouse model of immune damage (murine AIDS) and to try to find ways to overcome the damage of alcohol.
We chose first to study the effects of vitamin E supplementation. Let me add that while vitamin E supplementation does largely overcome the damage of alcohol to the immune system, in non-alcohol using mice, it further reduces tumor growth. Thus, the key is to avoid first any immune-damaging lifestyles and agents, like alcohol, then to try to optimize one's own situation with multiple antioxidant supplements.
Passwater: What does HIV do to the immune system?
Watson: It causes immune dysfunction with death to some cells (CD4+ T helper lymphocytes) and aberrant production of regulatory proteins called interleukins which shut down cellular defenses and cause humoral (antibody mediated B lymphocytes) to be stimulated but with little functional benefit.
Passwater: Recently, your research team has published results of your vitamin E and beta-carotene investigations. Would you please summarize them for us?
Watson: Our studies suggest that vitamin E and beta-carotene may be beneficial for treating HIV infection, but actual clinical trails are needed to confirm this hypothesis. Vitamin E stimulates the helper function and mitogenesis of T cells, and may enhance T and B cell action as well. We have found that vitamin E has increased the CD4/CD8 ratio, lymphocyte count, natural killer cell activity, phagocytosis, and mitogen responsiveness in both uninfected and retrovirus-infected mice. Vitamin E supplementation of normal mice at fifteen times the RDA increased a variety of immune functions. This applies to T and B cell functions which are suppressed by murine retrovirus infection. Vitamin E normalizes aberrant interleukin production in murine retrovirus-infected mice.
Also, of great importance, vitamin E restores tissue stores of both vitamin A and vitamin E that are reduced by murine retrovirus infection, and thus reduces the retrovirus-stimulated oxidative damage.
Our pilot study in HIV-infected persons showed that 30 milligrams of beta-carotene daily was not toxic and had immunomodulating effects. Three months of beta-carotene supplementation in HIV-positive persons increased immune markers in natural killer cells, but not in helper T cells.
Passwater: Vitamin E and beta-carotene are getting a lot of research attention these days, but what piqued your interest in Pycnogenol(R)?
Watson: We were asked to investigate a new antioxidant being used by humans, but unknown to me at that time, in our mouse models, as a favor to a colleague. We found that it had no negative effects on growth, food consumption, or immune functions in the mice. It stimulated several immune systems to some extent that were damaged by alcohol use or early retrovirus infection. The most significant finding was that it stimulated natural killer cell activity in uninfected, alcohol using, as well as retrovirus infected mice. Natural killer cells kill tumor cells and are the first line of defense against new tumors that arise in our body almost daily.
Passwater: I realize that your studies are continuing and will be submitted for publication shortly, but can you review some of the details that you presented in Biarritz?
Watson: We reported that Pycnogenol(R) enhanced the immune response of interleukin-2 in both retrovirus-infected mice and alcohol-fed mice. Pycnogenol(R) also reduced elevated levels of interleukin-6 and interleukin-10 during retrovirus infection and alcohol consumption. Natural killer cell cytotoxicity was increased with Pycnogenol(R) and this effect helped normalize the lost activity of natural killer cells during retrovirus infection. These changes are in the direction of returning a suppressed immune system back towards normal.
Immune dysfunction during LP-BM5 retrovirus infection is remarkedly comparable to HIV in humans: splenomegaly, lymphadenopathology, and hypergammaglobulinemia with progressive defects of T and B cell functions, and reduction of host resistance to pathogens and neoplasia. In HIV-positive patients and murine retrovirus infection T-helper 1 cells decline while interleukin-6 and interleukin-10 secretion by T-helper 2 cells increases. Murine AIDS, induced by retrovirus infection, develops into a progressive and profound immunodeficiency with loss of antioxidants as occurs in human AIDS.
T-helper 1 cells produce interleukins including interleukin-2 and gamma-interferon to induce cellular immunity, regulate cells and suppress interleukin production by T-helper 2 cells. Pycnogenol treatment of uninfected, normal mice did not cause a significant change in interleukin-2 production. Interleukin-2 production in mitogen-stimulated cells was significantly decreased by alcohol consumption and murine retrovirus infection when compared to cells from the uninfected control animals. In both instances, the production of interleukin-2 was significantly increased by Pycnogenol(R) when the cells were compared to those of the controls.
T-helper 2 cells produce interleukin-6 and interleukin-10 which suppress T-helper 1 cells, which is part of the immune dysfunction seen in murine AIDS. Supplementation with Pycnogenol(R) caused no significant change of interleukin-6 production by cells from normal control animals. However, Pycnogenol(R) exhibited a significant increase of interleukin-6 production in alcohol-fed mice when compared to untreated mice, with and without alcohol consumption. Our data also show that interleukin-6 production, which is significantly elevated during murine retrovirus infection, was significantly reduced by Pycnogenol(R) supplementation.
Mice given Pycnogenol(R) showed no significant change in interleukin-10 levels when compared to uninfected, normal mice. However, there was a significant decline in interleukin-10 production in alcohol-fed mice given Pycnogenol(R) supplementation when compared to alcohol-fed controls. A significant increase in interleukin-10 was observed for retrovirus infected mice. Interleukin-10 secretion by cells from alcohol-fed mice was not significantly different from that of uninfected normal mice. However, the level of interleukin-10 production by spleen cells from mice given Pycnogenol(R) supplementation during alcohol consumption, and retrovirus infected was significantly normalized when compared to uninfected mice not given treatment.
There was a dramatic increase in natural killer cell cytotoxicity for all three effector-to-target ratios in Pycnogenol(R) supplemented mice when compared to untreated mice. For the 100:1 effector-to-target ratio of retrovirus-infected mice, there was a significant decrease in natural killer cell activity when compared to the infected normal mice. This decrease was significantly normalized with Pycnogenol(R) supplementation.
Passwater: You have spent several years studying the effects of alcohol on the immune system and you have written extensively about your findings and the findings of other groups. Can you summarize your findings for us?
Passwater: We have investigated alcohol use in mice and people for 7 years, as well as getting numerous colleagues to summarize their research in 8 books on alcohol's actions on the body. The summation of all that work is that "ALCOHOL HAS NO REDEEMING BENEFIT AND ALMOST ANY IMPORTANT SYSTEM IN THE BODY IS DAMAGED TO SOME EXTENT BY ALCOHOL USE." We in particular found that alcohol use suppressed immune systems, especially when damaged by retrovirus infection, increased oxidative damage, reduced tissue nutrient levels in animals eating adequate diets, reduced lifespan, and promoted tumor growth. Colleagues have shown recently that alcohol use increases the susceptibility of cells to invasion and growth of HIV. My personal conclusion is to never drink alcohol for my personal health and as an example to my children of its extensive, slow damage to health.
Passwater: It is true that there have been at least a hundred epidemiological studies over the past thirty years that suggest moderate drinking has benefit. However, I have always contended that the significant health benefits come from the bioflavonoids and other polyphenolic antioxidants extracted from the stems, seeds and skins of the grapes, rather than the alcohol in the wine. Yes, there are studies that suggest that two sub-groups of high-density lipoproteins, HDL2 and HDL3, increases with alcohol consumption, but it is yet to be demonstrated that these sub-groups have the same protective effect as HDL1. Besides, the effect as measured is too small to account for the protective effect measured. This observed protective effect can be accounted for by improvements in blood platelet factors. There are also studies linking decreased blood levels of tissue plasminogen activator, but it is not clear that alcohol per se accounts for this change. Meanwhile there are other studies that show the bioflavonoids do promote health and longevity.
I remember a study nearly twenty years ago that compared the effects of drinking wine or wine in which the alcohol had been removed to a placebo of grape juice. The researchers found improvements in blood chemistries, including reducing the stickiness of red blood cells that encourages them to clump together (platelet adhesion indices), in the groups drinking either the normal wine or the alcohol-free wine compared to those who drank the grape juice. This indicated that the improvements came from the body of the wine that did not involve alcohol. Then a comparison was made between those who drank either grape juice or grape juice that had been spiked with alcohol, and no difference was observed in their blood chemistries.
An obvious factor is that both red wine and white wine have the same alcohol content, but it is only the red wine, with it's high proanthocyanidin (a branch of the bioflavonoid family) content that is significantly protective. Dr. Alexandra Lavy of Israel reported in 1994 that red wine boosts HDL by 26 percent, but white wine does not. Pycnogenol(R) is also rich in proanthocyanidins. Proanthocyanidins are the precursors of the red pigments found in red wine. Essentially the same types of grapes are used in making both red wine and white wine, but in making white wine, the "must" -- grape particles including skin, stem and seed particles -- are removed early in the process before they have a chance to color the liquid.
In several studies that show that moderate wine drinking has a protective effect, the drinking of beer or hard liquor do not show a health benefit at any consumption level. In fact a 1995 Copenhagen study shows that three to five drinks of hard liquor daily increases the risk of death by 36 percent compared with not drinking liquor.
Earlier this year, Dr. John Folts and his colleagues at the University of Wisconsin published a study that agrees with the premise that it is not the alcohol, but the bioflavonoids that provide health benefits. Dr. Folts is perhaps the premier researcher on blood platelet adhesion. In 1973, he developed the test that is still used today to test for impact on platelet adhesion. In 1974, Dr. Folts was the first to demonstrate aspirin's effect on blood platelets.
Dr. Folts and his colleagues have found that two six-ounce glasses of red wine daily significantly reduce blood plate adhesion. They have also found that drinking six six-ounce glasses of grape juice a day will produce the same results. Grape juice is made without the seed and stem extraction than wine.
Dr. Folts notes that red wine is high in the bioflavonoids quercetin and rutin. Dr. Leroy Casey of Cornell University has correlated the concentration of the bioflavonoid "resveratrol" with wine's protective effect. However, he finds more resversatol in concord grape juice than in most wines.
Sorry to digress, but I felt that some readers might like additional comment on this controversal subject.
Are your research findings on alcohol, ADIS and nutrition reaching practicing physicians and the public?
Watson: I am not sure, but I hope so. My message can be succinctly summarized. First, prevention is the key to health, so avoid situations that increase risk of HIV infection, immune damage (alcohol and drug use), and initiation of cancer (tobacco, sunlight, AIDS). Then take aggressive steps to promote health by increasing consumption of fruits and vegetables, and supplementation with antioxidant vitamins.
Passwater: Amen! Again science has backed my mother's teachings.
Passwater: What will we study next?
Watson: We will continue to try to optimize health for the aging adult. That will include continued investigations into the benefits of multiple antioxidant supplementation on immune and other systems. In addition, we are just beginning to investigate DHEA (dehydroepiandrosterone). This is a hormone that declines as we age simultaneously with development of immune dysfunction and increased cancer growth in the older and elderly populations. There is evidence in mice that DHEA supplementation will restore age-damaged immune systems which we are testing in older humans and mice.
All rights, including electronic and print media, to this article are copyrighted to Richard A. Passwater, Ph.D. and Whole Foods magazine (WFC Inc.).