During a prior 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
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
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
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
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
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
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.).
During a prior chat with Dr. Luc Montagnier, I mentioned the research