[Electronic distribution for GayCom by the Backroom 718 951-8256]

Volume 7 no. 11/12
 Winter, 1993/94

 Gay Men's Health Crisis: Treatment Issues 

 > An Alternative Treatment Activist Manifesto
 > Alternative Therapies for AIDS: An Historical Review 
 > Common Alternative Therapies
 > Understanding Vitamins
 > Traditional Chinese Medicine
 > Antioxidants, Oxidative Stress, and NAC
 > Evaluating New or "Alternative" Treatments
 > The Dietary Supplement Health and Education Act of 1993 (S.784/H.R.1709)

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An Alternative Treatment Activist Manifesto
 by Jon Greenberg 

This article was compiled and edited posthumously by Mary Beth
Caschetta, Rocco Giannetti, and Risa Denenberg from the writings of
Jon Greenberg, who died of AIDS on July 12, 1993. Jon was working on
this special edition at the time of his death. It was Jon's foremost
belief that true alternative treatment begins with self-empowerment.
"Information and self-empowerment are the sources of all our power
and ultimately the place from where all healing begins," he wrote not
long before his death. For more information on research advocacy for
alternative therapies write to the Treatment Alternatives Project 
c/o: the PWA Health Group, 150 West 26th Street, Suite # 201, New
York, NY 10011.

Since the beginning of the AIDS crisis, a number of "alternative"
medical treatments have been proposed and used with unknown success,
such as herbal compounds, nutritional supplements, traditional
Chinese medicine, as well as physical manipulation techniques and
spiritual approaches. Although these methods have all been lumped
together under the generic category "Alternative Health Care," they
differ substantially in philosophy, modality, cost, and other
important ways. However, they all share one unfortunate similarity -
virtually nothing is known about their activity in the human body and
their efficacy for treating AIDS.

The AIDS community tends to fall into two separate camps regarding
alternative therapies. Some dismiss all alternative treatments,
regardless of the evidence demonstrating efficacy, and others defend
all alternative treatments, regardless of evidence demonstrating
toxicity or lack of efficacy. The reality of most alternative
therapies probably lies somewhere between these two extremes. Some
alternative therapies may be effective, some are clearly ineffective,
and most possess some degree of toxicity. The chief difficulty with
using alternative therapies is a lack of empirical data and an
absence of scientific interest in these compounds. Presently, there
is no research infrastructure to address systematically the potential
benefits and risks of alternative treatments. 

Obstacles to Testing of Alternative Therapies

The goal of alternative treatment activists is to advocate for
controlled clinical trials of alternative treatments, so that
approval and acceptance can be gained for those treatments which are
found to be effective. Our goal is to make the term "alternative"
obsolete. At present, very few alternative treatments are ever 
studied in a government or university-sponsored clinical trial.
Because no funding exists for these projects, and because researchers
and other treatment activists have not made these concerns a
priority, most of the alternative treatments used by people with HIV
have never been tested. They have never gone through the process
which details their toxic effects in humans, assesses 
pharmacokinetics, bioavailability, safety and efficacy, and determines
their impact on the immune system. This situation is unacceptable,
especially considering that most substances which possess efficacy
also prove to have toxicities.

Since toxicity studies on most alternative therapies have not been
conducted - and since many alternative treatment practitioners often
recommend these therapies in very high doses - it must be asserted
that they may be toxic. For the most part, if a proponent of a
specific alternative therapy has observed negative side-effects,
there has been no mandate, no regulation, and therefore no
institutionalized reason to disclose such information. Additionally,
profit is as big a motive for the "alternative" medical community as
it is for the conventional pharmaceutical industry.

While some alternative treatment proponents have no financial
investment in proposed therapies, the emotional investment in the
therapy's success is usually high. Many alternative treatment
enthusiasts have a strong desire to prove conventional Western
medicine wrong. This sentiment sometimes precludes objective
evaluation. Very often, claims of efficacy and recommendations for
alternative therapies are based on anecdotal reports or loosely
designed observational studies. In fact, so far no study of an
alternative treatment in AIDS has been able to stand up to scientific
scrutiny. Design flaws, poor execution, or too-limited sample size
prevent these studies from generating useful or reliable information.

Making Decisions in the Information Vacuum

Every person with HIV uses a variety of methods to gather information
on treatment options. How much do I take? How often do I take it? Is
it a pure substance? What are the possible side effects? Will it
work? This decision-making process is complex and individual. And
controlled clinical studies of alternative treatments, although
necessary to gather scientific information, may ultimately yield
little useful information. Quite frankly, controlled clinical studies
are often open to interpretation and often raise as many questions as
anecdotal reports or personal histories do. 

Health care practitioners who share questions, doubts, criticisms
about treatment (as well as beliefs in a particular therapy), can
help people with HIV most by encouraging patients' responsibility for
his or her own decision-making process. People with HIV need to know
that doctors do not have all the answers. Right now, even with
empirical data about certain non-alternative therapies, there are
more questions than answers. Believing that doctors and orthodox
medicine holds the answers can be an obstacle to the self-empowerment
of people with HIV. The trust must come from within, not outside.  At
the moment, therefore, we are forced to make decisions without much 
information. To get the information we need will be a long process.

But it will be easier and more expedient to speak the language of the
researchers and the scientific community than it will be to force
them to speak the language of people with AIDS and treatment
alternative activists. It is also tiresome and sometimes confusing to
rely on other people's stories (not just doctor's stories) in order
to make a treatment decisions. As we all know, these stories are often
colored by biases and histories that we may not necessarily share.
This is not to say that these personal experiences are invalid for
those who believe and promote them. But each of us has a different
emotional, historical, psychological and intellectual make up.

Controlled clinical studies may offer the only opportunity to
evaluate directly treatment options from well-defined criteria. We
should not have to place extraordinary faith in one practitioner or 
theory of disease and treatment. We need answers to our questions.

It is important to identify through clinical studies those treatments
which seem most promising for testing and potential development. We
must make contacts among key researchers in pharmaceutical settings,
the federal government, research universities, and institutes across
the country. We must create an interest in the research establishment
to address the obstacles to research for alternative treatments. We
must learn how to write concept sheets, the blueprints for clinical
trials designs, to spark the interest of researchers. We must
strategize the best way to study the compound in question and the most
politically efficient manner to initiate study. This often involves
writing letters, making phone calls, and staging political actions to
urge all the parties involved to action. We need to get their
attention. Finally, all of the steps in this process must be
detailed, monitored, and documented.

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Alternative Therapies for AIDS: An Historical Review 
 by Carola Burroughs 

The use of unconventional, "alternative," natural, or complementary
therapies for AIDS, as for any other illness, has often been founded
in a frustration with the lack of safe or effective conventional
treatments: many people seek out unconventional therapies not out of
any intent to be different, but simply to find relief from problems
which conventional service providers either do not address or seem
unable to deal with adequately. In the case of AIDS, since for years
few drugs were even available, some PWAs sought out alternative 
treatments from the earliest years of the epidemic. Although advocates
of alternative therapies for AIDS have continued to push for wider
availability of and research into such treatments, they have been
very much a minority within the AIDS service community until quite
recently, when the vital role played by nutrition and oxidative
stress has finally begun to receive greater recognition, and the
results of the Concorde study, as well as the paucity of other
promising AIDS drug treatments seen at the last International
Conference in Berlin, have called into question the value of
conventional antiretroviral drugs.

The recent growth of interest in alternative therapies within the AIDS
community reflects an increase in attention on the part of the public
as a whole, as demonstrated by the results of the Eisenberg[1] study
which appeared in the January 1993 issue of The New England Journal
of Medicine. This study concluded that "the frequency of use of
unconventional therapy in the U.S. is far higher than previously
reported": a full 34 percent of the survey respondents reported using
at least one "unconventional" therapy in the preceding one-year
period, and the number of visits made to alternative practitioners
was estimated at 425 million, exceeding the number made to all U.S.
primary care physicians. The establishment of an Office of Alternative
Medicine at the National Institutes of Health in June 1992, by
Congressional mandate, is another indicator of the heightened
interest in investigating and validating alternative therapies.
However, not surprisingly, there remains a significant amount of
resistance and skepticism on the part of the medical establishment to
many unconventional therapies, whether for AIDS or any other
disorder. 

The term "alternative medicine" is a catch-all phrase which includes 
therapeutic nutrition, chiropractic, homeopathy, structural and
energetic therapies and mind-body interventions, traditional
ethnomedicinal systems such as Chinese medicine and Ayurveda which
combine botanical medicine with other applications, other uses of
non-Western and Western herbs, and various treatments which simply
have not been accepted by the medical establishment. Alternative
medicine has been variously called "natural," "complementary,"
"holistic," and numerous other terms which refer to elements of a
particular modality or tradition. "Complementary" is the preferred
term in Europe. The traditional ethnomedicinal systems are by nature
holistic, meaning that they aim to treat the whole individual, rather
than a specific disease or symptom, and that they address not only
the physical aspect of the patient but also mind and spirit. It is
assumed that each individual possesses an innate healing capacity
(the "immune system" in the broadest sense), and the goal generally
is to reinforce this capacity and restore strength and balance to 
weakened systems using a variety of natural modalities: foods, herbs
and other botanicals, body work, detoxification, etc., tailored as
much as possible to the individual's specific constitution and
condition. 

The use of alternative therapies for AIDS grew out of this same
eclectic mix. Traditional Chinese Medicine (TCM) and acupuncture, in
particular, became available for AIDS treatment early on in a number
of cities. At Lincoln Hospital in the Bronx, Dr. Michael Smith and
others who had participated in the development of the Lincoln
Hospital acupuncture project for drug treatment during the 1970s,
were in the forefront of AIDS treatment as well. In 1984 a number of
clinics and acupuncture centers in San Francisco and the Boston area
began to treat PWAs, and others followed. The Chicago AIDS Alternative
Health Project, founded in 1986, was the world's first acupuncture
clinic dedicated exclusively to the treatment of AIDS. The Institute
for Traditional Medicine in Portland, Oregon developed a series of
Chinese herbal formulas (the best known of which is Composition A)
which have been extensively followed since 1986 at ITM, at the Immune
Enhancement Project in San Francisco, and at the University of Miami.
Other aspects of TCM such as Qigong and Taiji (or T'ai Chi), are also
used for their proposed therapeutic benefits.

The Zen macrobiotic diet was another popular approach, particularly
for people with Kaposi's Sarcoma, and its use led to the 1982
founding in New York of Health Education AIDS Liaison (HEAL), the
oldest support and resource organization promoting the use of natural
and non-toxic therapies for AIDS. The development of a Western-based
version of Ayurvedic medicine, the traditional medicine of India, and
the Transcendental Meditation program, resulted in the founding of
Ayurveda Resources of New York, a resource and support group for
people with AIDS which employed meditation, herbal and purifying
massage therapies to enhance immune function.

Throughout the U.S., during the second half of the 1980s,
holistically-oriented MDs, OMDs (Doctor of Oriental Medicine),
chiropractors, and naturopaths, developed AIDS protocols combining
nutrition, Western and Asian herbology, acupuncture, homeopathy,
exercise, and mind-body approaches. Publications such as the Healing
AIDS newsletter, People with AIDS (PWA) Coalition Newsline, and John
James' AIDS Treatment News provided information and resource listings
about the growing body of treatment information.  Among other
widely-used treatment approaches, mind-body therapies were recognized
early on as an important aspect of immune enhancement. This area 
includes therapies such as meditation, imagery/visualization,
biofeedback, hypnosis, psychotherapy, expressive therapies (music,
art, and dance/movement), therapeutic and healing touch, and
spiritual healing. Organizations such as the PWA Coalition, Northern
Lights Alternatives, Body Positive, and the Center for Attitudinal
Healing offered workshops and seminars. The Manhattan Center for
Living, a companion organization to the Los Angeles Center for Living
founded in 1987 to offer support groups, body work, and other
life-supportive services for people dealing with any life-challenging
illness, but PWA/HIVs make up the bulk of their clientele.  Based on
the principles of A Course in Miracles, a channeled book which has
been called "a self-study course in spiritual psychotherapy," the Los
Angeles and Manhattan Center workshops and support groups emphasize
the healing power of meditation, love, and spiritual development.

Within the field of homeopathy, some practitioners and theorists began
early to consider the challenges presented by AIDS, but within the
homeopathic community as a whole, unfortunately, little progress has
been made in achieving consistently beneficial results. Effective
treatment with classical homeopathy depends to a great degree on the
skill and experience of the practitioner. Since there is no standard
licensing and hence no protection for homeopaths nationally, many
fear legal reprisals. 

In Seattle, Bastyr College of Naturopathic Medicine's Healing AIDS
Research Project (HARP), begun in October 1988, is assessing the
results of protocols combining Chinese and Western botanicals or
classical homeopathy with nutrition, hyperthermia, and other
therapies. The earlier-mentioned research efforts of projects
affiliated with the Institute for Traditional Medicine continue, in
San Francisco, Chicago, Santa Fe, and Los Angeles. There have been and
continue to be a number of small, community-based clinical trials of
single substances such as lentinan (shiitake mushroom) and St. John's
wort (hypericin). 

As for research efforts at the fledgling Office of Alternative
Medicine, with its miniscule $2 million budget, two out of the
initial thirty grants awards are for AIDS projects, both to look at
the potential immune-boosting effects of massage, on preterm newborns
of HIV-infected mothers and on patients with advanced AIDS. In
addition, the OAM has initiated another non-funded research track in
the form of field investigations of alternative practitioners. Two of
the practitioners who are being considered for this program are doing
work in AIDS, Dr. Charles Simone with shark cartilage for KS, and Dr.
Jon Kaiser with a multiple-modality nutritionally-based protocol for
HIV/AIDS generally. An historical review of alternative approaches to
AIDS treatment would not be complete without mentioning issues of
access. Alternative medicine, despite its roots in traditional
ethnomedicine, has the not-undeserved reputation of being new age and
only for the elite or middle-class. This, however, is due to its 
fringe status, which makes it mainly unreimbursable by insurance and 
entitlement programs, rather than to any lack of interest on the part
of low-income people. As alternative medicine gains wider acceptance among
the medical and insurance industries, as for example in the case of
Dr. Dean Ornish's program for cardiovascular disease, it will also
become more available to the population at large.

1. Eisenberg et al, "Unconventional Medicine in the United States; Prevalence, 
Costs and Patterns of Use," NEJM, 1/28/93, 246-252.


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Common Alternative Therapies
 by Bree Scott-Hartland
 
Acemannan (CARRISYN)

Acemannan (trade name Carrisyn) is a freeze-dried powder form of
juices extracted from the aloe vera plant. Aloe vera has been used
for centuries for its healing properties, especially for burns. Some
pre-clinical experiments have suggested that Carrysin may have both
antiviral and immunomodulatory effects in vitro.[1] Manufactured by
Carrington Labs in Irving, Texas, Carrisyn has been studied in PWAs
in a number of clinical trials.

Canadian researchers conducted a randomized, placebo-controlled study
evaluating 400mg of Carrisyn (four times a day) as an adjunct to
antiretroviral therapy (AZT or ddI) in 62 HIV-positive individuals
(CD4 counts between 50 to 300). It was hoped that Carrisyn would
enhance the efficacy of AZT and ddI. No serious side effects were
observed, although there were reports of nausea, vomiting, and
abdominal pain. After 48 weeks, no difference was seen in regard to
either CD4 count or p24 antigen level.[2, 3]

Another trial in 47 HIV-positive individuals with no symptoms or ARC 
concluded that Carrisyn is well tolerated and non-toxic but had no
effect on modifying the toxicity of AZT.[4]

Studies conducted on behalf of the manufacturer found that of 41
patients given Carrisyn (250mg, four times daily) in several
different studies[5, 6], 24 had a 10 percent or greater increase in
absolute CD4 cell levels, a reduction in p24 antigen levels, and a
reduction in their Walter Reed clinical classification score. Those
with CD4 cell levels above 150 cells and p24 antigen levels less than
300pg/dL had better response rates than those with lower CD4 and
higher p24 levels. 

There is no evidence that aloe vera juice has sufficient levels of
acemannan to provide any anti-HIV or immunostimulatory effect. Aloe
juice can, however, cause diarrhea.

1. McDaniel HR, et al. Abstract p-121. American Society of Clinical 
Pathologists. 1987.

2. Ruedy J, et al. Abstract PuB 7488.VIII International Conference on AIDS. 
1992.

3. Singer J, et al. Abstract PO-B28-2153. IX International Conference on AIDS. 
1993. 

4. Weerts D, et al. Abstract S.B. 469. VI International Conference on AIDS. 
1990.

5. McDaniel HR, et al. Abstract S.B. 493. VI International Conference on AIDS. 
1990. 

6. McDaniel HR, et al. Abstract 3566. IV International Conference on AIDS. 
1988.

See Also:

Gingell B. Treatment Issues. 1987; 1:2. Korsia S. IHITTG. 1991; 5:3.


ARTEMISIA

"Artemisia" or Qing Hao (Artemisia annua) has been used as an
anti-malarial herb in China since before 340 A.D. More recently, an
extract of the herb, artemisinin or qinghaosu (QHS), has shown
efficacy againstmalarial.[1] 

In the test tube, concentrations of QHS (0.4 micrograms/ml for five
days) inhibited Toxoplasmosa gondii in human fibroblast cells.[2] At
a dose of 1.3 micrograms/ml for fourteen days, T. gondii was
completely eliminated. Cells exposed to this dose for up to 27 days
showed no toxic effects. Six derivatives of QHS showed equal or
greater activity. QHS has also shown activity in test tube and animal
studies against other human parasites, such as Schistosoma 
species.[2] 

The World Health Organization and the U.S. Department of Defense are 
currently developing QHS and its derivatives as anti-malaria
therapies; the Ou- Yang study suggests that these compounds may also
have a place as anti-toxoplasmic agents.

1. China Cooperative Research Group on Qinghaosu and Its Derivatives as 
Antimalarials. Journal of Traditional Chinese Medicine. 1982;2:31-38.

2. Ou-Yang K, et al. Antimicrobial Agents and Chemotherapy, 1990; 34:1961-65.

ASTRAGALUS

"Astragalus" (Astragalus memranaceious), is an herb used in China,
reportedly for the purpose of "boosting" the immune system and
preventing chemotherapy-related bone marrow suppression and nausea.
In the former Soviet Union and Japan it is used to treat heart
attacks and strokes.[1] The active substances are taken from the root
of the plant. This non-toxic herb should not be confused with
Astragalus lentiginosus, a related but more toxic plant. 

It has been reported that an extract of Astragalus, Fraction 3 (F3), has 
stimulated immune responses in the test tube and in animal studies. In
one study, injections of F3 into rats treated with the
immunosuppressive drug cyclophosphamide resulted in the rats
rejecting grafts of foreign tissue.[2] In the test tube, F3 improved
the anti-tumor activity of Interleukin-2 (IL-2) in human 
lymphokine-activated killer cells.[3] In another test tube study[4],
an Astragalus decoction, (obtained by boiling the ground root in
water), increased the proliferation of lymphocytes taken from healthy
people and cancer patients. A team at Loma Linda University in
California used a similar method to obtain an extract that increased
the activity of human macrophages in the test tube.[5] Both teams
reported that the observed effects decreased at higher doses.[4, 5]

Since no clinical trials of Astragalus in people have been performed,
it is unknown whether the effects seen in the test tube can be
duplicated in the body. The dose and route of administration are
known. 

While Astragalus is believed to be non-toxic, there are reports that
it can trigger low blood pressure and increase the amount of urine
produced, resulting in a feeling of dizziness and fatigue.[6] In
addition, the Loma Linda team warned that over-dosing of Astragalus
may cause immuno-suppression, and that herbs from different sources
may vary in quality and produce differing results. 

1. McCaleb R. Better Nutrition. 1990; October: 22-23,32.

2. Chu DT, et al. Journal of Clinical Laboratory Immunology. 1988; 25:125-29.

3. Chu DT, et al. Journal of Clinical Laboratory Immunology. 1988; 26:183-187.

4. Sun Y, et al. Journal of Biological Response Modifiers. 1983; 2:227-237.

5. Lau BHS, et al. International Clinical Nutrition Review. 1990; 10:430-434.

6. Korsia, S. IHITTG. 1992; 7:3-4.


BITTER MELON (MAP-30)

"Bitter Melon" (Momordica charantia) is the fruit of a vine-type
climbing plant and is a relative of Chinese Cucumber (Tricosanthes
kirilowii), the source of the drug Compound Q. Extracts of Bitter
Melon fruit, seeds, and vine have been used in Asia to induce
abortion and as a treatment for diabetes, gastrointestinal
complaints, and some cancers and viral infections.[1] Scientists have
identified several active proteins extracted from Bitter Melon,
including MAP-30, alpha-momorcharin, and beta-momorcharin. 

In the test tube, MAP-30 inhibited the ability of HIV to infect cells
and to replicate, as assessed by expression of the HIV core protein
p24 and by levels of reverse transcriptase in certain cell cultures.
It also inhibited syncytia formation.[2] No toxic effects on human
cells were seen in these assays. A crude extract from Bitter Melon
fruit has shown anti-tumor activity in mice[3], and a seed extract
inhibited herpes virus-1 and poliovirus in human cells.[4] 

Since 1988, PWAs in the U.S. have experimented with retention enemas
using juice and tea extracted from the bitter melon plant. Anecdotal
reports of the effects range from those who had sustained CD4 cell
level rises[5] to those who showed no effect. Recently, the Los
Angeles community-based trials group SEARCH Alliance proposed a
clinical trial of MAP-30 in PWAs; however, the National Institutes of
Health (NIH) declined to fund the study, citing "problems with
toxicities over long-term use."[6] 

1. Cunnick J et al. Journal of Naturopathic Medicine. 1993; 4:16-21.

2. Lee-Huang S, et al. Federation of European Biochemical Society. 1990; 
272:12-18.

3. Jilka C, et al. Cancer Research. 1983; 43:5151-5155.

4. Foa-Tomasi L. et al. Archives of Virology. 1982; 71:322-32.

5. Zhang QC. Journal of Naturopathic Medicine. 1992; 3:57-61.

6. Astudillo RM. Bay Area Reporter. May 27, 1993.


BLUE GREEN ALGAE (Spirulina) 

"Blue-green algae" (Cyanobacteria) is a generic name for algae found
in most wet places. Spirulina is a variety commonly available at
health food stores. In August 1989, scientists at the National Cancer
Institute (NCI) reported that extracts from L. lagerheimmi and P.
tenue, two specific types of blue-green algae found only off the
islands of Hawaii and Palau, contained sulfolipids which inhibited
the cytotoxic (cell-killing) effects of HIV and reduced HIV 
replication in the test tube.[1] Attempts to grow these specific
strains in the laboratory failed, and an expedition to collect
further samples was stopped by the U.S. Marines off Hawaii.[2]
 
It is unknown whether Spirulina contains such sulfolipids. It has not been 
shown to possess any direct benefit against HIV, though it is rich in amino 
acids and minerals. 

1. Gustafson KR, et al. Journal of the National Cancer Institute. 1989; 81:1254P
1258. 

2. James J. AIDS Treatment News. 1989; 87:1-2.


COENZYME Q10 

First isolated in cow heart cells, Coenzyme Q10 (CoQ10) is found in 
mammalian tissue, with the highest concentrations in the heart, liver,
kidney and muscle. CoQ10 levels are abnormally low in people with
congestive heart failure, and in populations with HIV, muscular
dystrophy, periodontal disease, immune dysfunction, and
immunosuppression caused by the cancer chemotherapy doxorubicin.[1]

CoQ10, which is widely used in Japan, was first tried against heart
disease by Per Langsjoen. Langsjoen claimed improved cardiac out-put
and stroke volume in heart patients treated with CoQ10.[2]

Folkers and colleagues tried 200mg of CoQ10 a day (oral) in three
persons with AIDS and four persons with ARC. Though only one patient
completed the seven-month protocol, Folkers reported on five who
stayed on CoQ10 for a minimum of four months. T4:T8 ratios for three
patients in this small cohort reportedly improved.[3] 

No toxicities have been reported from CoQ10 use.

1. Henderson CW. AIDS Therapies. 1993.

2. Folkers K. in Coenzyme Q, , G. Lenaz, ed. John Wiley & Sons Ltd., 1985, 
pp. 457-478.
3. Folkers K, et al. Bioc Biop Res Com. 1988; 153: 888896.


COMPOUND Q (GLQ223)

"Compound Q" is an extract of Tricosanthin, a type of cucumber native
to China. It has been used for the past twenty years in China to
induce abortions and treat malignant tumors. GLQ223 is a highly
purified derivative of Trichosanthin GLQ223 is now being developed by
Genelabs Inc. of Redwood City, CA. 

Early test tube studies of Compound Q in the winter of 1988/89 caused
great excitement among PWAs, due to the agent's ability to
selectively inhibit HIV replication in infected T-cells and
macrophages. These studies reported that GLQ223 suppressed HIV
reproduction as measured by p24 antigen levels[1]; similar results
were obtained by the same researchers using the whole blood from PWAs
in later studies.[2] 

In May 1989, Project Inform and three other groups began a clinical
trial of Compound Q injections for AIDS. Some participants, mainly
those with the most severe illness, encountered major toxicities,
including progression of Kaposi's Sarcoma, coma and death. Other side
effects included muscle pain, joint pain, swelling, rashes and hives,
all of which resolved upon cessation of treatment.[3, 4 ]

An FDA-approved Phase I trial at San Francisco General Hospital
reported fewer serious toxicities in single, rapid IV transfusions of
GLQ223 at doses ranging from 1 to 36 micrograms/kg of body weight.
The anti-HIV activity was not of sufficient duration for an antiviral
effect, however.[4, 5] 

A Phase II study of GLQ223 in 148 persons with AIDS or ARC with 200 to
500 CD4 cells who had been taking AZT, began in 1991. Patients were
randomized to three arms: AZT, GLQ223, or AZT and GLQ223. Side
effects included flu-like symptoms, elevations in muscle and liver
enzymes and allergic reactions. There was no difference among the
three arms of the study in the time to treatment failure (defined as
greater than 25 percent decline in CD4 levels, development of a new
AIDS-defining infection, or death).[5]

1. McGrath M, et al. Proceedings of the National Academy of Science (US.), 
1989; 86: 2844-48.

2. McGrath M, et al. abstract S.B. 464-6.VI International Conference on AIDS. 
1990.

3. Waites LA, et al .abstract S.B. 466.VI International Conference on AIDS, 
1990.

4. Kahn J, et al. AIDS. 1990; 4:1197-1204.

5. Kahn J, et al. abstract S.B. 465.VI International Conference on AIDS. 1990. 

6. AIDS Weekly. November 1, 1993, p3-4. 

see also:

Armington K. Treatment Issues. 1990; 4:5.


CURCUMIN

"Curcumin" is the main active ingredient found in turmeric, a spice
used primarily in curry. It is responsible for the unique yellow
coloring of foods with curry. A study published in the March 1993
Proceedings of the National Academy of Sciences. evaluated three
substances, including curcumin, for anti-HIV properties.[1] The two
other substances analyzed were topatecan, which is currently being
tested as a cancer treatment, and beta-lapachone, which has not been
tested in humans, although lab and animal data suggest human dosages
are possible.

The study reviewed many substances for a new class of compounds that
would inhibit the Long Terminal Repeat (LTR) of HIV (LTR is believed
to be critically important to turning on and maintaining HIV
replication). These three compounds emerged as the most promising
candidates that would inhibit the LTR.

Results suggested that topotecan was the most powerful anti-HIV
compound and was well tolerated in cancer patients. Curcumin was less
effective, but important because it is consumed readily in food and
available to a broad  range of populations. There is, however, no
clear evidence, at this time, that curcumin has any real benefits
other than as food coloring and flavoring. The third compound,
beta-lapachone, had no human toxicity information available, but
seems well tolerated in animal studies.

1. Proceedings of the National Academy of Sciences, March 1993; 90:1839-
42.



ECHINACEA

The leaves and root of "Echinacea" (Echinacea angustifolia or E.
purpurea) have been used by Native Americans for a broad range of
pains and illnesses. Broad immunostimulatory effects have been
attributed to the herb. Advocates of echinacea have pointed to test
tube and animal studies to support these claims.[1]

Test tube studies conducted in Germany showed that purified extracts
from echinacea stimulate T-cells and macrophages1 and may have
anti-viral properties.[2]

In a clinical trial in Germany, fifteen patients with colorectal cancer were 
injected with 60mg/square meter of body area of echinacin (a purified extract of 
Echinacea) and thymostimulin after initial treatment with cyclophosphamide, an 
immunosuppressive drug.[3] Tumor regression was noted in two patients after 
two months of therapy, and disease stabilized in six others. (This stabilization 
was possibly part of the natural course of the disease, however.) Echinacin 
was also reported to have stimulated macrophages to release chemical 
messengers such as TNF-a (Tumor Necrosis Factor-alpha), IL-1 (Interleukin-1) 
and Interferon beta (IFN-b). This and other studies[4] also noted that echinacin 
may have helped increase the number of CD4 cells relative to CD8 cells within 
three days after cyclophosphamide treatment.

An additional study found that the administration of Echinacea
extracts to people stimulated cell-mediated immunity after a single
dose, but that repeated daily doses suppressed the immune
response.[5]

Injections of purified Echinacea are believed to be relatively
non-toxic, even at high doses[6], although there are reports of skin
rashes and insomnia.[7] 

Unfortunately, few clinical trials have been performed using either
injected polysaccharides or oral, over-the-counter Echinacea
supplements, which are the most common form of this remedy.
Therefore, the effects and ideal dosing of this remedy are unknown. 

1. Foster S. Echinacea: Nature's Immune Enhancer. Rochester, VT: Healing 
Arts Press, 1990.

2. Wacker A, et al. Planta Medica, 33, 89-102, 1978.

3. Lersch C., et al. Cancer Investigation. 1992;10:343-48.

4. Wiseman C, et al. Proc. AACR. 1989; 30:412.

5. Coeugniet EG, Elek E. Onkologie. 1987;10(suppl.3):27.

6. Luettig B, et al. Journal of the National Cancer Institute. 1989;81:669.

7. Korsia, S. IHITTG. 1992; 7:3-4.



GARLIC

Garlic (Allium sativium), a member of the lily family, has been used
for medicinal purposes from as early on as 3,000 B.C. It is made up
of sulfur compounds, amino acids, minerals like germanium, selenium
and zinc, and vitamins A, B and C. Allicin, a sulfur containing
compound in garlic, is believed to be primarily responsible for most
of the suggested benefits of garlic - along with the unique odor.

Garlic has been used for many medicinal purposes in folk and holistic
treatment for heart disease, hypertension, heavy metal toxicity and
is now being looked at for immunotherapy. A review of the literature
on garlic appeared in The Journal of the National Medical
Association. The clinical and basic studies suggested a broad
spectrum of potential uses.[1] 

Animal models have demonstrated that garlic may be a non-specific
biologic response modifier[2]. Some researchers have postulated that
garlic works as an antioxidant against free-radicals because of its
germanium and selenium content.[3] A 1951 study in Science described
how mice injected with cancer cells died within sixteen days, but
when mice were treated with garlic extract no deaths occurred in the
mice for six months.[4]

Claims of garlic's effectiveness against AIDS-related opportunistic
infections are based on test tube studies that showed garlic was an
anti-bacterial,[5, 6] and anti-fungal agent.[7, 8] There have been no
studies as yet that have looked at garlic closely for its uses with
immunomodulation, but protocols are constantly being written and
submitted by community researchers and activists.

Toxicity with garlic usage occurs when too much raw garlic is
ingested. The high sulfur content can cause dermatitis; and colitis
occurs by an overkill of the normal flora in the gut. In high doses,
garlic also may inhibit blood clotting and interfere with proper
thyroid function.

1. Abdullah TH, et al. Journal of the NMA. 1988: 80:41.

2. Lau, B, et al. Journal of Urology, 1986; 136:701-05.

3. Pierson, H. Oral Presentation. Conference on Oxidative Stress in HIV/AIDS. 
November 8-10, 1993 Bethesda, MD.

4. Weisberger AS. Science.126:1112, 1951.

5. Cavallito CJ, et al. Journal of the American Chemical Society. 1945; 
67:1032-33.

6. Johnson MG, et al. Applied Microbiology. 1969; 17:903-5.

7. Tansey MR et al. Mycologia 1975; 67:409-413.

8. Yamada Y, et al. Antimicrobial Agents and Chemotherapy. 1980; 11:123-6. 

see also:

Doostan D. "The stinking rose: a clove a day keeps the doctor away?" IHITTG. 
1992; 7.



GERMANIUM-132

"Germanium-132" (Ge-132) is a mineral composed of the elements
germanium, oxygen, carbon, and hydrogen. High levels of the mineral
are found in ginseng, and high levels of the element germanium are
found in garlic, comfrey, and watercress. Ge-132 is claimed to have
immunostimulatory and antioxidant properties.

In an animal study, oral administration of Ge-132 stimulated
production of gamma-interferon (gamma-IFN) and activation of
macrophages and natural killer cells.[1] In humans, Ge-132 has been
claimed to affect T- and B-cell function, natural killer
proliferation, and other immune functions.[2] An abstract at the IX
International Conference on AIDS in Berlin reported that "organic" 
germanium may act synergistically with alpha interferon in inhibiting
HIV in the test tube.[3]

Currently, germanium is available on the market at most health food
stores. While some sources suggest a dose of 100mg taken three times
a day, there are currently no human trials completed or planned for
AIDS or HIV-related illness, so the efficacy and dosage of Ge-132 are
unknown. Ge-132 has no known toxicities.

1. Aso H. Microbiology and Immunology. 1985; 29:65-74.

2. Henderson CW. AIDS Therapies. 1993.

3. Narovlyansky A, et al. Abstract PO-A13-0240.IX International Conference 
on AIDS. Berlin. June 1993. 



GINSENG 

Ginseng root is an herb that has been used extensively throughout
Southeast Asia and China for various treatments. There are three
different families of ginseng: the Oriental and American ginsengs
("Panax ginseng"), the Siberian ginseng (Eleutherococcus senticosus),
and the desert ginseng (Rumex hymenosepalus). For thousands of years,
Ginseng has been considered by many to be the most prized of herbal
remedies, containing a host of alleged benefits including
anti-fatigue, anti-stress, and other systemic benefits.  It has been
suggested that Panax ginseng may increase natural killer cell 
activity. In a double-blind, human trial, trial subjects were given
standardized doses of 100mg Panax ginseng in capsule form every
twelve hours for eight weeks.[1] Among other parameters, T8 and T4
cells were looked at, but there was no significant change in either
the placebo group or the group receiving the capsules.

Mice given immunosuppresive doses of cyclophosphamide also showed 
increases in Natural Killer cell activity after Panax ginseng.[2]
Panax and Eleutherococcus can produce insomnia, diarrhea,
nervousness, depression and skin rash. Ginsengs can amplify the
effect of certain anti-depressant medications and, due to the small
amount of estrogens in the plant, can affect menstruation in
women.[3]

1. Scaglione F, et al, Drugs Under Experimental and Clinical Research, 1990; 
16(10):537-42.

2. Kim JY, et al. Immunopharm. & Toxiciology, 1990; 12(2):257-76.

3. Korsia, S. IHITTG. 1992; 7:3-4.



GLYCYRRHIZIN (LICORICE ROOT)

Glycyrrhizin is a substance isolated from the root of the licorice
plant (Glycyrrhiza radix). It is widely used in Japan and is reported
to have benefits in the treatment of chronic hepatitis B. Some
studies suggest that glycyrrhizin may have anti-HIV properties[2] and
may enhance the production of natural killer cells and interferon.[3]

Japanese researchers recently studied the effects of a glycyrrhizin
compound Stronger Neo-Minophagen C (SNMC) in 42 HIV-seropositive
hemophiliacs.[4] Participants were randomized to dose regimens of
either 100 to 200ml or 400 to 800ml administered intravenously daily
for the first three weeks and every second day for the following
eight weeks. Absolute CD4 counts and CD4/CD8 ratios were unchanged.
However, "complete recovery in liver dysfunction," a major problem in
HIV-positive hemophiliacs, was reported. The authors conclude that
HIV-infected hemophiliacs with impaired immunological ability and
liver dysfunction be given prophylactic treatment with SNMC to prevent
their conditions from worsening. 

At the IX International Conference on AIDS in Berlin, two small,
non-randomized studies of glycyrrhizin in asymptomatic HIV-positive
individuals suggested some benefits to the treatment.[5, 6] However,
these studies, both of which were conducted in Japan, are difficult
to analyze or draw any conclusions, due to the small size and the
extremely limited data that were published.

There are reports of glycyrrhizin causing high blood pressure, water
retention, and possibly heart complications when taken in very high
doses.[7]

1. Fujisawa K, et al. Asian Medical Journal. 1989; 23:754-56.

2. Hattori T, et al. Antiviral. Res., 1989; 11(5-6):255-61.

3. Ito, M, et al.Antiviral Res., 1988; 10:289-98

4. Mori, K, et al. Journal of Naturopathic Medicine, 1993; 4:2-9.

5. Ikegami N, et al. Abstract PO-A 0596. IX International Conference on AIDS 
June 1993. Berlin. 

6. Yasuyuki E, et al. Abstract PO-B28-2143. IX International Conference on 
AIDS. June 1993. Berlin. 

7. Korsia, S. IHITTG. 1992; 7:3-4.



GREEN BARLEY LEAF EXTRACT

The dried extract of young barley green leaves ("green barley leaf
extract") is widely used in Japan and other countries as a
nutritional supplement. Green barley leaf extract (GBLE) is reported
to contain high levels of superoxide dismutase, a potent
antioxidant.[1] 

Studies of GBLE, almost all of which have been conducted in Japan,
suggest possible in vitro anti-inflammatory and anti-leukemic
activity, and reduced healing time of ulcerous lesions in rats.[2]
Other studies have reported anti-oxidative, anti-inflammatory,
anti-allergic, anti-carcinogenic, anti-ulcer and anti-viral
properties of barley green extract.[3] It has been suggested that GBLE
may increase production of Interleukin-2 when added to cell
cultures.[3] IL-2 is a protein produced by the body, which may have
immune boosting properties and seems to decrease with progression to
AIDS. Researchers at San Francisco General Hospital have suggested
that there may be an anti-HIV substance in barley green extract.[4]
This study was done in conjunction with the Japan Pharmaceutical
Development Company, a manufacturer of GBLE (brand name "Green
Magma").

An unblinded, uncontrolled study in 38 non-HIV infected patients with
skin disorders (eczema, atopic dermatitis) reported that four grams
of GBLE in water, three times per day resulted in an overall
"response rate" of 75 percent of patients.[5] No side effects were
reported. GBLE is considered rich in chlorophyll and a number of
studies have suggested that chlorophyll may have a beneficial effect
on chronic pancreatitis.[6] Another study of 24 patients with chronic
pancreatitis in Japan suggested that GBLE was "fairly effective" in 
eight cases (33 percent, "somewhat effective" in ten cases (42
percent) and "not effective" in six (25 percent) cases.[7] 

Researchers at St. Vincent's Hospital in New York City, in conjunction
with the Hagiwara Institute of Japan, are developing a protocol for a
Phase I study of GBLE in twelve HIV-positive individuals.[8]

1. Hagiwara Y. Study of Green Juice Powder of Young Barley Leaves. The 
98th Annual Assembly of Pharmaceutical Society of Japan. 1978.

2. Kubota K, et al. Japanese Journal of Inflammation .1983;3;4.

3. Matsuola Y, et al. Japanese Journal of Inflammation. 1983, 3:602.

4. Mazeika G, et al. Effects of green barley leaf extract on HIV-a infection in 
vitro. In press.

5. Muto T. New Drugs and Clinical Application. May 10, 1977;26(5).

6. Oda T, et al. Gastroenterology Japan. 1971; 6:49.

7. Yokono O. Therapeutic effect of water-soluble form of chlorophyll-a and the 
related substance (young barley green juice) in the treatment of patients with 
chronic pancreatitis. Faculty of Medicine. University of Tokyo.

8. Barr M. "Safety and bioavailability of green barley extract in HIV-infected 
persons: a phase I nutritional study (final draft protocol)." October 1993.



HYPERICIN

"Hypericin", an extract of the St. John's Wort (Hypericin perforatum)
plant, is believed to inhibit the replication of cells already
infected with HIV.[1] Other test tube studies suggest that hypericin
works to inactivate HIV virions or interferes with either the
assembly or shedding of viral particles.[2] This mechanism may be
synergistic with AZT or other reverse transcriptase inhibitors. Used
in Germany in the 1940s as an anti-depressant, hypericin appears
non-toxic, though photosensitivity (discomfort to exposed light) has
been reported from it in both animals and humans.

A U.S. clinical trial of intravenous (IV) hypericin (manufactured by
VIMRx Pharmaceuticals of Stanford, Connecticut) in HIV-infected
individuals began in November 1991. However, the trial, conducted at
New York University Medical Center (NYU), was temporarily closed
because of significant photosensitivity in patients receiving 2mg of
hypericin twice a week. The trial was restarted and preliminary
results were released at the First National Conference on Human
Retroviruses in 1993. A new dose of hypericin (0.25mg/kg twice or
three times per week) was initiated in 25 patients with less than 300
CD4 cells. Dose limiting toxicities (photosensitivity) were again
seen. No significant change in viral load was observed.[3] 

A trial of VIMRx's oral formulation is planned to start at NYU in the
beginning of 1994. For information, call Janet Vacariello at (212)
263-8724.[4]

Extracts of St. John's Wort plant, in oral formulation, are available
in many health food stores. However, there is no evidence that these
compounds provide any benefit as an anti-HIV therapy.

1. Valentine F et al. Abstract WA 1022. VII International Conference on AIDS, 
Florence. June 1991. 

2. Meruelo D et al. Proceedings of the National Academy of Sciences .1988; 
85:5230-4.

3. McAuliffe V, et al. Abstract 570. First National Conference on Human 
Retroviruses. Washington, DC. December 1993. 

4. Personal Communication. Trip Gulick, MD. January 3, 1994.



ISCADOR 

Iscador is a trade name for an extract of European mistletoe (Viscum
album). Used since the 1960s in Europe as an anti-cancer agent,
Iscador is purported to possesses both anti-tumor and
immune-stimulatory properties.[1]

A 1986 study of Iscador in breast cancer patients showed drug
dependent increases in red and white blood cells which returned to
baseline 72 hours after treatment.2 In the same year, a study against
disseminated cancer showed cytotoxic (cell killing) activity from
Iscador as well as immune stimulation.[3]

In 1989, University of California researcher Robert Gorter reported
that Iscador has "significant anti-HIV activity" in the test-tube.[4]
Anecdotal reports published that year on the use of Iscador in
PWA/HIV mentioned benefits including CD4 and natural killer cell
increases, weight gain, and regression of KS lesions.[5] Some toxicity
including painful welts at injection site and fever were reported 
from Iscador use. Toxicity appears to be largely dose dependent. 

A German study, released as an abstract at the IX International
Conference on AIDS in 1993 examined the use of iscador in 40
HIV-positive patients with less than 200 CD4 cells.[6] Patients
injected themselves, subcutaneously, with .01mg to 10mg of Iscador
twice per week for eighteen weeks. The only toxicities were transient
fever on day of injection and soreness on injection site. The 
researchers of this small, unblinded, and unreviewed study reported
that 28 of the 36 patients (77 percent) had increases in CD4 levels
of greater than 20 percent.

However, a 1991 study found that Iscador stimulated expression of
Tumor Necrosis Factor (TNF) in human monocytes and macrophage
cultures from mice.[7]

Iscador should only be administered under the supervision of a doctor
familiar with its use. 

1. Khwaja TA, et al. Oncology. 1986; 43(supp 1):42P50.

2. Hajito T. Oncology. 1986; 43(supp 1):51P63.

3. Salzer G. Oncology. 1986; 43(supp 1):66-73.

4. Palazzolo J, Baker R. BETA. 1988; November: 6P7.

5. Smith D. AIDS Treatment News. 1989; December: 5P6.

6. Gorter R, et al. Abstract PO-B28-2167. IX International Conference on AIDS. 
Berlin. June 1993. 

7. Mannel DN. Cancer Immunology and Immunotherapy. 1991; 33:177P82.

see also:

Smith D. "Iscador: promising experience to date." AIDS Treatment News. 1989; 
92.



Lactobacillus Acidophilus

Lactobacillus acidophilus (L. acidophilus) is the most well known of
a type of acidophilus bacteria (bacteria attracted to acid). It has
been suggested that L. acidophilus is a beneficial or so-called
"friendly" bacteria which provides an important function in the body.
Live cultures of L. acidophilus can be found in a number of brands of
yogurt or acidophilus milk and in the form of powders, capsules,
tablets and liquids which are available in health food stores. L. 
acidophilus is measured by the amount of viable bacteria per dosage
(in the millions). 

Test tube studies have shown that L. acidophilus can inhibit the
growth of candida albicans (candidiasis ), the fungus associated with
"thrush" in the mouth, esophagus or vagina.[1] Varying levels of
success have been reported using yogurt and L. acidophillus as a
treatment for vaginal candidiasis.[2, 3] 

A study conducted by researchers at Long Island Jewish Hospital and 
published in the Annals of Internal Medicine, reported that women with
recurrent vaginal candidiasis who consumed eight ounces a day of
yogurt high in L. acidophilus had a threefold reduction in number of
candida infections and laboratory measured candida colonizations.[4]
The authors of this report also noted that a number of dairy products
did not contain the L. acidophilus that had been advertised on the
label. 

Some suggest the use of L. acidiphilus to reimplant friendly bacteria
into the gastrointestinal system. A number of physicians routinely
suggest that patients undergoing antiobiotic therapy, consume eight
ounces per day of yogurt with L. acidophilus. It has also been
suggested, based on test tube studies that L. acidophilus may have
potential antiobiotic effects of its own.[5] There have been no
reports of L. acidophilus related toxicities; however, it is unknown
whether the compound has any effects on the absorption of anti-biotic
medication.


1. Isenberg HD et al. Factors Leading to overt monilial disease II: retardation of 
growth of canidida albicans by metabolic end products of intestinal bacteria. 
Antimicrobial Agents Annual. New York. Plenum Press. 1960.570-5.

2. Will TE. The Lancet. 1979; 2:482.

3. Sandler B The Lancet. 1979; 2:791-2. 

4. Hilton E, et al. Annals of Internal Medicine,.1992; 116:353-357.

5. Friend BA, et al. Journal of Applied Nutrition. 1984. 36:125-153



Milk Thistle (Silymarin)

The seeds of "milk thistle" or, silybum marianum, have been considered
by some to have liver protecting properties. Proponents of milk
thystle point to the British herbalist Culpepper who suggested the
ingestion of milk thistle roots and seeds for jaundice (a yellow
pigmentation of the eyes and skin which may indicate liver
disfunction).[1]

Silymarin is an extract of silybum marianum. In 1983, it was reported
that when Silymarin was given to rats with part of their livers
removed, some liver regeneration occurred.[2] It has also been
reported that silymarin provides protection against the ingestion of
certain substances which are extremely toxic to the liver or kidneys,
such as the deadly Amanita mushrooms.[3]
 
Proponents of milk thystle suggest that the compound can be used for
liver-based problems including cirrhosis, jaundice, hepatitis,
weakened liver due to drugs, alcohol, and liver poisoning from
chemicals, and diarrhea. Some reports have suggested that silymarin
may stimulate certain immune functions[4] and may protect the liver
during hepatitis B.[5] A reportedly randomized, controlled study in
170 patients with cirrhosis of the liver concluded that silymarin 
provided benefits in terms of mortality.[6] Other reports, mostly out
of Germany, suggest that silymarin may provide benefits in the
treatment of acute and chronic hepatitis B, in terms normalization of
liver functions.[7] However, the texts of these studies have not been
carefully examined. 

PWAs often have lower levels of glutathione. Therefore, it may be of interest 
that one study has suggested that silymarin protected against glutathione 
depletion induced by acetaphinomen in rat livers.[8]

No studies of milk thistle in PWAs with liver conditions could be
found. No toxic effects of silymarin have been reported, although it
is possible that because of its purported effect on the liver and
kidneys, the compound may effect the absorption of other medications.
Silymarin is available in health food stores in tablet form.

1. Hobbs C. Milk Thistle: The Liver Herb. Botanica Press. Capitola, CA. 1992.

2. Vogel, G. Proceedings of the International Bioflavonoid Symposium. p 472. 
1991. Munich.

3. G Vogel. " Natural Substances with Effects on the Liver" New Natural 
Products and Plant Drugs with Pharmacological, Biological, or Therapeutical 
Activity" p. Springer-Verlag. 1977. New York:.

4. Deak G. Orvosi Hetilap. 1990: 24:1291.

5. Chan MK. Nephrol Dial. Transplant . 1989; 4:297-301.

6. Ferenci P, et al. Journal of Hepatology. 1989:9:105P113.

7. C. Milk Thistle: The Liver Herb. Botanica Press. Capitola, CA. 1992.

8. Campos R. Planta Medica. 1989; 55:417P419, 420-22.


PCM-4

PCM-4 is a product combining two components purported to have 
immunomodulating effects. The two components are an extract ("P") from
the porcine spleen and a highly concentrated form of Siberian
ginseng.

The oral dosage of these two extracts was developed by Dr. Nicholaus
Weger in Munich, West Germany in 1987. The pill was developed after
initial studies done with Siberian ginseng suggested that the
combination might be capable of increasing T-cells.[1] Other studies
from as long ago as 1965 had shown that patients with cancer of the
stomach who experienced immune suppression had general improvement
with the use of the porcine spleen extract, the polypeptide or "P."

There are reports of some studies in HIV-infected people being
conducted, but these studies are either incomplete or have not been
published. 

PCM-4 is available at health food stores in drops, tablets and
capsules and is recommended at about 100mg per day with meals. No
toxicities of PCM-4 have been reported, but it is suggested that the
compound not be used by those with high blood pressure.

1. Brown, D.J., "PCM-4: New Standard of Excellence in Immunomodulation," 
Health Store News, Oct./Nov. 1991.



PRUNELLIN

In 1989 researchers from the University of California, Davis, isolated
the active component of the herb Prunella vulgaris and named it
"Prunellin."[1] The herb is a member of the family "Labiatae", which
is commonly known as "Self-heal" and was once used to treat cuts and
wounds.

Test tube studies with Prunellin blocked cell-to-cell transmission of
HIV. Polymerase chain reaction (PCR) showed in vitro that cells
exposed to HIV in the presence of Prunellin remained completely
uninfected. Researchers from Lady Davis Institute for Medical
Research suggested that Prunellin exerted an anti-HIV effect by
preventing the virus from binding to cells.

Other in vitro studies suggested that Prunellin also inhibited reverse
transcriptase because of its content of anionic polysaccharides that
are know to inhibit reverse transcripase in such drugs as heparin.[2]

1. Tabba H.D, et al. Antiviral Research, 989; 11:263-73.

2. Henderson CW. AIDS Therapies. 1993.



SHARK CARTILAGE

Shark cartilage is rich in an angiogenesis inhibiting protein called
Cartilage- derived Inhibitor. Angiogenesis is the process whereby new
blood vessels are formed to feed cancer, particularly solid tumors,
such as Kaposi's sarcoma.[1, 2]

In June 1992, a small community-based study of shark cartilage as a 
monotherapy treatment for Kaposi's sarcoma (KS) in PWAs was begun by 
SEARCH Alliance in Los Angeles. Preliminary anecdotal results reported
by Dr. Fleischman of the group were disappointing. Of thirteen
patients, only six were evaluable at study's end. A dose of 60 grams
of shark cartilage was administered by retention enema two to four
times a day. This means of administering the compound proved to be
impractical so patients took the same dose orally. Patients reported
an "extremely foul taste" and nausea associated with therapy. There
was no discernible regression of KS lesions after two to three months
of follow-up.

1. Lee, A. and Langer, R. Science 221:1185P7.

2. Oikawa T, et al. Cancer Letter. 1990; 51:181P6.

2. Fleischman, E. SEARCHLIGHT March/April, 1993:2.


SHIITAKE MUSHROOMS

Shiitake Mushrooms (Lentinan edodes) are a traditional Oriental herbal
remedy (and currently a popular haute cuisine ingredient) and being
used in the process of making LEM (Lentinan edodes mycelia). LEM is
the active component incubated in water to allow digestion of
mycelial enzymes. The digest of mycelia enzymes is extracted with
water, filtered, sterilized and concentrated into a powder. The LEM
powder is put into ethyl alcohol and freeze-dried to become
ethanol-precipitated LEM or E-P-LEM. 

Japanese researchers report that pretreatment of T cell cultures with
.4mg/ml. E-P-LEM protects them from both free-viral and cell-to-cell
HIV infection without cell viability. Pretreatment of HIV with a
.5mg/ml of E-P-LEM made it unable to infect cells at all. The
researchers suggest that E-P-LEM interferes in HIV interaction with the 
cellular CD receptor. 

These were test tube studies done in Japan, however, and as yet there
are no human trials planned in the US.

1. Tochikura TS, et al. Med. Microb. & Immun., 1988; 177:235-44.



SHO-SAIKO-TO (SSKT)

Sho-Saiko-To (SSKT) is a central formula in Chinese medicine. It is
readily available in many countries in Asia. While SSKT is a
combination of seven ingredients in precise proportion, the most
active component is speculated to be Scutellariae from which
"baicalein" is derived. Baicalein has been synthesized in a highly
purified form and is being investigated at the National Cancer
Institute. 

Researchers from Columbia University analyzed the effect of SSKT on 
lymphocytes from HIV-infected individuals.[1] The results showed a
greater inhibition of HIV reverse transcriptase and reductions in P24
antigen levels in HIV-seropositive asymptomatic people than in people
with ARC. No significant viral inhibition was found in people with
AIDS.

Dosages have been suggested at 3 to 15 grams a day, but without
clinical studies, dosing becomes difficult, to say the least.
Toxicities have not been reported even at levels of 15 grams a day in
studies with animal models. In a poster presentation at the V
International Conference on AIDS, Japanese researchers reported
"immunological improvements" in seven of thirteen patients with HIV
infection and relatively low CD4/CD8 ratios.[2]

In a review of SSKT as a potential anti-HIV therapy, Notes from the 
Underground, the newsletter of the New York-based People with AIDS
Health Group, concluded that "at present, we believe insufficient
data exists to support self-medication with SSKT".[3]

1. Watanabe K, et al. abstract MCP 148. V International Conference on AIDS. 
1989. 

2. Fujimaki M, et al. abstract WBP 292. V International Conference on AIDS. 
1989. 

3. Ravitch M. Notes from the Underground. 1992. 17:1-2. 


 ^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^
 ^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^

TI Interview: Jane Buckle

Jane Buckle is the Director of Research Coordination at the Research
Council on Complementary Medicine in London, a private British
charity that conducts and advocates for research on alternative
medicine. Derek Link spoke with Ms. Buckle on November 30, 1993, in
New York City. 

TREATMENT ISSUES: What is the RCCM? What is its mission? 

BUCKLE: The RCCM was set up ten years ago by a group of physicians and
alternative practitioners who felt that one of the best ways forward
for alternative medicine was through rigorous research that would
stand up to scientific nitpicking. Our mission is to encourage,
initiate, and oversee rigorous research into all alternative
medicine. 

We are a privately funded charity and we are not government aided like
the Office of Alternative Medicine here. [Editor's note: the OAM is a
government funded program which is part of the National Institutes of
Health.] And so we've managed to maintain neutrality - total
neutrality. We are nonpromotional. And we are nonderogatory. We just
want rigorous research into all alternative medicines. 

This has enabled us, if you like, to act as brokers between orthodoxy
and nonorthodoxy, and to be brokers between government and what they
feel the patient wants and what the patient wants. Over the last ten
years, we've funded over 1 million pounds' worth of research into
alternative medicine. This ranges from a fellowship in homeopathy to
very small pilot schemes looking at Alexander Technique and musicians
and acupuncture on chronic pain and sickle cell anemia. 

TI: Let's talk a little more about funding. You mentioned that the
RCCM doesn't receive government money. What is the role of the
industry in funding the RCCM? In America, we now are having a debate
about the proper role of the dietary supplement and alternative
health industry in funding research into their products. What is the
situation in Britain?

BUCKLE: The funding of the RCCM, as it's a private charity, comes from
private individuals and corporations. We just have to go cup in hand
and say, "We've been given a research protocol on whatever, and we
feel this merits research funding. Will you fund it?" So we have
specific funding for specific things. There are certain organizations
or people who will fund us to to look into their pet thing, if you
like. Like acupuncture, homeopathy, whole medicine or whatever. Or
they may fund us to go into education. They may fund a conference or
workshop on methodology or they may fund the existence of our actual
organization. 

TI: What should the pharmaceutical industry be doing?

BUCKLE: The pharmaceutical industry is obviously looking more and more
for more products, because they need more money to generate profits,
and it's an ongoing treadmill. Having said that, where would we be
without many of the drugs which they have very carefully tried to
promote? We need things like penicillin. We need antibiotics. We need
a great many of these things. Where would we be without the
contraceptive pill? We would survive, yes, but life is greatly
enhanced by these "terrible" pharmaceutical people. It would be nice
to think that they could fund projects as groups of pharmaceutical
companies. So you would have the three or four biggest in America
banding together and talking to each other and saying, "Right. Even if
it's only philanthropic, we're going to chuck in together in view of
our total budget. Let's do this. Let's the four of us actually band
together and say we are going to underwrite trials into this to see
whether this works." 

Because just say, for example, they discovered acupuncture helps
something or other. Then that might just trigger off something to
them which they could then develop - not acupuncture, but they might
realize through their research what endorphins gone off, what
neurochemical has gone off.

The pharmaceutical industry could perhaps do a little lateral thinking
rather than invest just totally in new chemicals - which are still
needed - then, maybe this is the way that everybody can actually work
together.  If one could actually change the name of the
pharmaceutical company or drug company to a health-oriented company -
one of the sections of which is pharmaceutical - then maybe you could
change the perception of how they are seen and how they see
themselves. It's all too easy to get into "them and us." And as I've
said, they've saved a great many lives. They will probably save a
great many more lives. 

TI: Could you define alternative therapy and describe its role in
medical care? 

BUCKLE: I would suggest that maybe the alternative approach, the 
complementary approach is looking at another angle. I view orthodox
and nonorthodox medicine as yang and yin. On their own, I would
suggest that they would be much stronger together. Much stronger
together. I would very much feel more comfortable with alternatives
as being viewed complementary to the orthodox system.

Different approaches can come together and you have the yang and yin.
One could suggest that perhaps a complementary medical approach is a
more feminine approach, a more intuitive, a more spiritual, a more
emotional nurturing approach than the yang which is the mechanistic,
male, we're-going-to-kill-the-bug approach. It's not that either is
better than the other. I think together, then there is a very good
marriage and a very good possibility of holistic looking at someone's
health. And in the end it should be for the patient to feel what is
appropriate for them. 

If you were to have a heart attack you wouldn't want me to waft
lavender over you. On the other hand, there comes a point when people
are chronically ill, they don't want anymore drugs tried out on them.
They don't want any more things. They perhaps want their wholeness to
be nurtured and to allow the terrain of their health to change. And I
think very much complementary medicine has been nurtured and been
made more acceptable by the AIDS community, who wanted a holistic
approach. They realized that there was something missing and they
wanted a more holistic, not one or the other.

I would suggest that an alternative therapy is that which is outside
the norm of the country in which you are at that particular time. If
what we're talking about here is a traditional medicine which is
traditional to the country of origin, where it's actually standard,
it is orthodox for that system. So for example, traditional Chinese
or Japanese medicine is traditional in that country. They've had it
for thousands of years, they don't need to validate it. But when you
export a system that's traditional to another culture, it becomes an
alternative to the medical system of that country. I would like to
suggest that we don't view it as alternative, but we view it as
complementary to what we have grown up and expect. 

So what would be an alternative in China would not be acupuncture
because they have a dual system over there. They have MDs and they
also have acupuncturists. An alternative medicine is that which has
been taken out of its own culture and put somewhere else and then
people will look on that instead of their own orthodox training.

I would suggest that possibly one of the big problems of removing a
philosophy from the country of origin, is that something is lost in
the moving. And this is particularly so of traditional Chinese
medicine which is not just acupuncture. It's acupuncture and herbs
and a particular form of drawing the blood to the surface. There's a
particular form of massage, there's a particular form of meditation -
tai ch'i, relaxation and there are five or six parts of it which in 
China you get together. Then acupuncture has arrived in the West
without all those. Now it's a little bit like saying well, we'll have
antibiotics but we won't have anything else. Or we'll have
antidepressants, and we wouldn't have anything else. How sure can we
be that that can work on its own? That it doesn't need the synergy of
the other ones?

TI: One of the most difficult issues in treatment education is to
instill in lay people the concept of a risk-benefit ratio. Many
people seem to believe that alternative equals non-toxic or
risk-free. Of course, this is wrong. The toxicities 
 of many alternative products are not known. Other products,
particularly some herbs, are known to be toxic. In the absence of
research into these products, how would you suggest that somebody
evaluate the risk-benefit ratio of a given alternative therapy? 

BUCKLE: I think the way is to have a specialist group who knows what
each discipline is trying to achieve and the possible side effects,
counterproductive effects. For example, if you were to look at - pick
one.

TI: Let's say Chinese medicine.

BUCKLE: Chinese medicine. If we were to take Chinese medicine, then
you could analyze what Chinese medicine is, roughly, it's one of
these six things. You'll most likely come across these. Your
therapist can be an MD trained in acupuncture for a few weeks, an MD
trained in acupuncture for months, years or somebody who's trained in
acupuncture but not an MD. What are the initials after his name mean?
So you instantly know how long that person has been trained for. 

What is the treatment likely to consist of? How long? How will it make
you feel? What is it not going to do? How is it most likely to
benefit you? From the pain? From the depression? Sleep? Relaxation?
Is there research to substantiate this or is this just anecdotal? If
it's anecdotal, how many people have said this and in how many
states? And, is this for all acupuncturists or just acupuncturists in
San Francisco or New York? What are the possible toxic effects of
taking the drugs? Can you take the drugs and mix them with the
western drugs that you're taking? 

And I think to stress, stress, stress that whatever complimentary
therapy your clients are taking, they must tell their MD even if
their MD is openly hostile. Because the only way that the two are
going to talk to each other is by educating your MD as well as the
patient. But if your MD is actually trying something out on you to
see whether it's working and you're doing all sorts of other things,
he's never going to know what's working and what isn't. 

TI: There is another element to the alternative therapy world,
because, of course, it is a multi-billion dollar industry which is
essentially unregulated. We get a letter every other day about
somebody has some new "cure," which costs $10,000 and is only
available by going to clinic X. What's your advice to somebody who's
looking at the whole panoply of possible therapies? How do you
determine the legitimate from the suspicious? How do you smell a
fraud? 

BUCKLE: Well, if someone was to advertise that I was going to be
younger tomorrow if I took this pill, and it would cost me a million
dollars, I wouldn't believe it. If they're telling me that I was
going to take a pill and I'd lose lot of weight, I wouldn't believe
them. So I think if something is being pushed as being very expensive
and definitely working, I would be extremely suspicious. As in all
things, I tend to go by recommendation. I would go to a specialist 
doctor because he had been recommended by somebody who'd been who 
found the doctor helpful. This presumably, because you're in the
health business, is exactly the way that you would go.

There will be specific therapies which will be more inviting to
particular people. And just go, go where you feel you need to go. HIV
people are like everybody else. They have different symptoms - they
don't just have one symptom. They will possibly have one or two
symptoms which individually to them is really what they can't bear.
Okay. Well, go to a therapy which suggests that it might help this
and just see. If one therapy doesn't work and you feel like trying 
another, try another. 

One of the problems with complimentary medicine in the UK is not much
of it is available on the NHS. Some of it is, but not much. And it
becomes very expensive. So you need to budget. How many times can I
go and see this acupuncturist? When will I expect a difference? And
do this before you go. This is an investment you're making in your
health. 

Okay, so I have $200 that I'm going to invest to try and improve my
symptoms, my quality of life, my life span. I'm going to go to this
person, because somebody has recommended them. Take it. Do your own
"research" each time. And when you come back - is it helping the
diarrhea? Is it helping the sleep? It is helping the sweats? What is
it doing? Is it doing anything? And then do your own evaluation. Do
your N=1 study. Your own research study. And if everybody did lots
N=1, and we put them all together, we might have some very
interesting statistics which we then could give to people to get
proper funding. So, initially, you can actually begin your own
research strategy by doing that.

TI: How is prognosis viewed in alternative medicine and what role does
should that play in developing methodologies for research? For
instance, one of the issues that I found most interesting was in a
book on Chinese medicine that said it was "weak on outcomes" Could
you comment on prognosis in alternative medicine - is it a weakness
or just a difference? 

BUCKLE: I could comment but I think what I would like to do before I
comment is to actually explain the difference as I see it. This is a
personal view point of someone who is trained in both the orthodox
system the alternative system. Western mechanistic medicine goes into
fight an infection and kill it, and the person will be better.
Alternative medicine suggests that people would not have succumbed to
an infection unless there had been a hole in their wholeness. And
therefore, if you replace homeostasis, the ability of someone to
actually cure themselves of a common cold or heal a cut, or a broken
leg to mend, if you enhance that, then the disease won't have a
footing, and therefore it will go. So alternative or complementary
medicines seem to be more appropriate in chronic conditions rather
than acute conditions. If someone has a heart attack, they need
Western medicine. But if somebody was to have a chronic condition, 
perhaps say arthritis, one could perhaps look at the disease from both
perspectives. It's something that Western doctors find difficult to
accept and it's something that alternative practitioners find very
difficult to accept.  There is also the ethical situation of viewing
disease as one's pathway through life, that we aren't all
super-healthy every day. Is there a reason for getting a particular
disease at a particular time? And disregarding serious AIDS, cancer, 
heart attacks and things like that - colds, flus, this sort of thing
- if that is your pathway, is it ethical to actually take that away
from someone so they don't learn that lesson.

In Western medicine we put great stock on getting somebody back to
work. So we will ram them full of this, that and the other
hypertensive drug to get their blood pressure down, make them sleep,
etc., etc. so they'll carry on exactly the same - same food, same
stress, same whatever, which one could argue was precipitating the
terrain that caused the problem. And then it will probably happen
again and again and again. 

TI: Thank you very much for your time.

 
 ^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^
 ^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^

Understanding Vitamins
 by Derek Link

INTRODUCTION

Vitamins are a diverse group of chemically unrelated compounds,
present in food at minute levels, that are necessary for normal human
function. By definition, the deficiency of a vitamin causes disease.
Minerals are also critical to human life in minute amounts and they
differ from vitamins only in that they are inorganic. (Organic in
this case refers to the chemical meaning "composed of carbon," not
"grown naturally" in the popular sense.) This article reviews basic
background information on vitamins and minerals and examines several 
individual vitamins that are frequently discussed in the context of
HIV. 

Vitamin Requirements

An adequate diet supplies all required vitamin and minerals to a
healthy individual. However, vitamins and minerals are unevenly
distributed among different food sources. The 1976 Nationwide Food
Consumption Survey estimated that most Americans obtain over 80
percent of their vitamin intake from 50 to 200 foods. As a result,
several "core foods" have been identified that are particularly rich
sources of vitamins. (See table I below.) 

Vitamin and mineral requirements are established in the United States
by the Recommended Daily Allowance (RDA) guidelines, a familiar item
on food and dietary supplement labels. Contrary to popular belief,
the RDA is not developed for prescriptive use nor do they establish
target vitamin and mineral intakes for individuals. Wide individual
variation exists in vitamin and mineral requirements. The RDA only
provides standards for population studies of nutritional status and
reference values for food labeling. 

The RDA is the upper limit of a range of values which has a highest
probability of fulfilling the nutritional requirements of most
Americans. Any one individual may have a unique requirement within
the range of intakes. There is a very small probability that an
individual will have a required intake above the RDA level.[1]

The RDA is established in populations of healthy, normal subjects. It
is unknown if vitamin and mineral requirements differ substantially
in a population of people with HIV, although infection may impact
vitamin requirements, according to studies of other populations. 

Biology Poorly Established

Although most vitamins were discovered over 50 years ago, still very
little is known about their biological role. Vitamins are clearly
essential to life, yet the full range of their biological effects and
their mechanism of action is poorly established. Nutritional
immunology (the study of the role of vitamins and minerals in
immunity) is still in its infancy and many unanswered questions 
remain. For instance, Vitamin A has a well characterized role in
vision, where it serves a critical function as a signal mechanism
between the retina and the initiation of nerve impulses. (Vitamin A
deficiency, considered one of the most serious nutritional public
health problems in the world, is the leading cause of preventable
blindness, primarily among children in high risk areas, such as India
and east Asia.) Yet vitamin A also has a role in cell differentiation
and thus is important in immunity, although it is poorly understood.
Furthermore, the biological connection between specific vitamin
deficiencies and their diseases is also unknown. For example,
riboflavin deficiency clearly causes cracked lips and tongue, but the
biological pathway that leads to these symptoms is unknown. More
puzzling still, vitamin deficiency diseases seem to manifest 
themselves differently in different parts of the world for unknown
reasons. For instance, thiamin deficiency is primarily associated
with peripheral nerve disease in Asia, but central nerve disease in
the Western hemisphere. Much progress is needed in understanding the
biological role of vitamins.

HIV-Related Deficiencies

Studies of nutrient levels in people with HIV find that they are
either depleted, increased, or unchanged. These studies are difficult
to interpret since they were not performed in a uniform manner and
were often inadequately controlled. It is important to note that the
literature on vitamin deficiencies does not even point in a
consistent direction. Most discussion of vitamins, however, center on
research that suggests nutrients are depleted, rather than unchanged
or increased. 

Overt signs of severe vitamin deficiency can be detected by clinical 
examination. However, most reported vitamin deficiencies in people
with HIV are mild and subclinical, based primarily on variations from
population norms in laboratory diagnosis. There are several
confounding factors to consider when interpreting this level of
deficiency. 

Population norms of vitamin levels are sometimes based on estimated
values, and thus may not be accurate. People with HIV may constitute
a distinct population and may have different vitamin requirements
than the normal, healthy population. Several studies indicate that
metabolism may be altered in HIV disease, possibly changing nutrient
requirements. However, no studies have been performed that
demonstrate unique nutrient requirements in people with HIV. 

Correlating mild deficiencies to clinical signs or increased risk of
disease is difficult and poorly established. According to the
published reports, mild laboratory-diagnosed deficiencies may
indicate early signs of progressive malnutrition, a response to
specific infections, nutrient-drug interactions, altered metabolism,
inadequate diet, or random errors on imperfect lab tests. Although
all these conditions have been documented in people with HIV, it is 
unknown to what degree they each contribute to specific nutrient
deficiencies on an individual level. 

Diagnosis

Diagnosis for most mild vitamin and mineral deficiencies is
technically complex and may be open to considerable variation among
laboratories. There are two distinct methods of biochemical diagnosis
of vitamin deficiencies. One method involve examining vitamins (or
their metabolites) in blood, urine, or tissue samples. These levels
are compared with a population reference range for the nutrient,
which, as described earlier, may or may not reflect the nutrient needs
of HIV-infected people. 

The other method of diagnosis involves loading tests of vitamins and
tests of enzymatic function. While these tests do not need population
reference ranges, and are considered more reliable by some, they are
routinely available. The acute phase response (APR) may also affect
observed vitamin levels. The APR is a set of metabolic changes,
induced by cytokines such as Interleukin-6 (IL-6) and Tumor Necrosis
Factor (TNF), which naturally occur in response to infection, cancer,
or inflammation. Observed nutrient may be considerably altered during
the APR because they are sequestered in intracellular compartments.
Whether deficiencies observed during the APR are functional or just
signs of altered vitamin metabolism and circulation is unknown. 

Hair analysis is a method of diagnosis used by some physicians and 
alternative health practitioners. However, hair analysis is not an
established, validated method for clinical practice. It is primarily
a research tool and may have some use detecting heavy metal poisoning
in populations. Hair analysis is not reliable for individual nutrient
analysis for several reasons. Vitamin and mineral levels in hair have
not been correlated to the clinical or biochemical condition in the
body. Hair care products and other environmental factors may also
impact vitamin and mineral levels in hair. Furthermore, some reports 
suggest that hair analysis laboratories are not standardized, with
wide variation among them. At its worst, some authors suggest that
hair analysis is more a marketing tool than a method of diagnosis. In
some cases, even healthy people are told to purchase many types of
vitamin supplements based on hair analysis diagnosis of "deficiency."

Vitamin Supplementation

At present, there is no convincing evidence that vitamin and mineral 
supplements positively impact on progression of disease or death in
people with HIV. No well-controlled studies have examined the
relationship between supplements and disease in people with HIV.
Universal recommendations for specific supplementation regimens in
people with HIV are, therefore, based on speculation and uncontrolled
anecdotes. 

The presence of a vitamin or mineral deficiency does not imply that 
supplementation will correct it. Deficiencies may be caused by many
factors, including some which may not respond to supplementation.
HIV-induced metabolic changes or malabsorption can result in vitamin
deficiency, although they will not respond to supplementation.
Importantly, several studies demonstrated vitamin and mineral
deficiencies in people with HIV although the subjects ate properly
and, in some cases, even took supplements. Furthermore, correct
vitamin and mineral doses are not been established to correct
specific levels of deficiency. 

Mega-Dosing 

Beneficial claims are frequently for very large doses of vitamins
("mega-dosing"), often hundreds or thousand times higher than
nutritionally required levels. Using vitamins in this manner is more
similar to drug therapy than nutrition, and should be considered in
pharmacological terms. Some "mega-doses" of vitamins may have
legitimate pharmacologic uses, although none have been demonstrated
for HIV disease. Certain vitamins, like Vitamin A and Vitamin D,
produce very serious toxicities not far above their nutritionally 
required levels. Other vitamins, like Vitamin E, appear to have no
upper limits for safe consumption. (See table II below.)

Vitamin A and beta-Carotene

Vitamin A (and beta-Carotene - a pro-vitamin that is converted into
vitamin A by the body), first discovered in 1915, is found in both
animal and plant products. Vitamin A has a role in many physiological
functions, including reproduction, skin, vision, the immune system,
and bone. Vitamin A deficiency can cause numerous non-specific signs,
although nyctalopia and xerophthalmia (two diseases of the eye) are
the best described syndromes. Vitamin A deficiency is considered
extremely rare in the developed world because many common foods,
including margarine, are fortified with the vitamin, and because the
body can store Vitamin A successfully in the liver and intestine for
long periods of time, compensating for periodic deficiencies. 
Diseases associated with vitamin A deficiency occur only after
prolonged periods of deprivation. 

Vitamin A and The Immune System

Numerous studies have documented that Vitamin A has a critical role in
the function and differentiation of many cell types, including immune
cells, although its mechanism of action is undefined. 

Animal studies indicate that vitamin A deficiency causes immune system
dysfunction and pathology. Chickens that are experimentally infected
with Newcastle disease virus (a serious respiratory and nervous
disease in fowl that can cause transient conjunctivitis in humans),
when fed a diet deficient in Vitamin A, show increased pathology and
an altered disease pathogenesis.[2]
 
Another study of chicks infected with Newcastle disease virus
demonstrated that immunoglobulin levels were decreased during vitamin
a deficiency.[3] Rats infected with Angiostrongylus cantonesis (a
parasitic disease, transmitted by shellfish, that causes a lung
infection in rodents and may infect humans) show increased
susceptibility and more disease when deprived of Vitamin A.[4] 

Chicks infected with Escherichia coli have decreased resistance to
infection and an altered immune response when fed diets either high
or low in Vitamin A.[5] Vitamin A-deficient rats have impaired
phagocyte activity during bacterial infection.[6] Antibody synthesis
and T cell proliferation are increased in chickens supplemented with
Vitamin A.[7] Finally, lymphoid organs appear atrophied and
underdeveloped in Vitamin A-deficient rats.[8]

Several clinical studies of Vitamin A deficiency and supplementation
confirm that also has a role in human immune function. The most
convincing study of the benefits of Vitamin A supplementation on
reduced infections and mortality was conducted in India, where
deficiencies of the vitamin are common.[9] The well-designed, blinded
study enrolled 15,419 preschool children in an area of Southern India
where Vitamin A deficiency is common. They were randomized to receive
weekly Vitamin A supplements (8333 IU) or Vitamin E (20mg) for over
one year. The study reports a startling 54 percent reduction in
childhood mortality, primarily through reductions in diarrhea and
infections. An editorial in The New England Journal of Medicine that
accompanied the article said that "the available evidence now
supports the immediate implementation of Vitamin A programs in
specific cases - wherever there is evidence that a population has a
vitamin a deficiency, wherever protein-energy malnutrition is common,
and wherever there is an excess of measles deaths."[10]

Other clinical trials have pointed to the same conclusions about
Vitamin A supplementation in high-risk populations, although they
were not as large nor as well-designed as the Indian study. An
Australian study of 147 young children found that daily vitamin A
supplements reduced the incidence of respiratory infection compared
with placebo.[11] A randomized study of 450 villages in Sumatra (an
Indonesian Island) found that children in villages randomized to
receive one or two vitamin a supplements (200,000 IU) over several
months had a 50 percent reduction in mortality compared with children
in villages which received placebo.[12] A South African study of 189
young children hospitalized with measles found that vitamin a given
in a total dose 400,000 IU reduced the length of recovery from
pneumonia and diarrhea, shortened hospitalization, and improved
survival compared with placebo.[13]


Vitamin A and AIDS

Vitamin A deficiency may occur in people with HIV through an unknown 
mechanism, according to several preliminary reports. Vitamin A
deficiency may be secondary to an overall state of protein-energy
malnutrition in people with HIV or could be related to the host
response to infection. Infection and fever increase the metabolism of
Vitamin A, increase its urinary excretion, impair its intestinal
absorption, and can diminish hepatic stores of the vitamin, all
leading to systemic deficiency.[1]4 Vitamin A deficiency may lead to 
increased risk of infection and further vitamin deficiency, leading
several investigators to describe this relationship as a "vicious
cycle."[15, 16, 17, 18]
 
However, serum vitamin A levels may be affected by the APR, so serum 
diagnosis is difficult and can not be considered definitive.  A study
from Baltimore examined serum Vitamin A levels in 179 intravenous 
drug users (126 HIV-infected, 59 uninfected).[19] Fifteen percent of
the HIV-infected people had serum levels consistent with Vitamin A
deficiency. Overall, the infected group had lower mean plasma levels
of the vitamin compared with the uninfected controls. Vitamin A
deficiency was associated with lower CD4 counts and an increased risk
of mortality. An abstract presented at the 1992 International AIDS
Conference found that people with HIV were more likely than
historical, uninfected controls to have lower serum vitamin A levels
and deficiencies.[20] Vitamin A levels were only partially associated
with decreased dietary intake in this study. Serum vitamin A levels 
were also reduced in 18 percent of asymptomatic HIV-infected people, 
according to a 100-person study from the University of Miami.[21]

Despite growing evidence that vitamin A deficiency can occur in some
people with HIV, the mechanism(s) of the deficiency and the clinical
significance of this finding are unknown. Furthermore, it remains
unclear if vitamin A supplementation can reverse the deficiency and,
more importantly, improve the clinical outcome of patients. This
uncertainty is increased by evidence that Vitamin A can both increase
and decrease HIV replication, depending on cell type, in vitro.[22,
23]

Vitamin B-6 (pyridoxine)

Vitamin B-6 (discovered in 1934) is crucial to many biological
processes, including, most importantly, amino acid metabolism and
biosynthesis. Vitamin B-6 is found in most foods, but meat provides
the most usable form of the substance. White bread, and other grains,
are often fortified with the vitamin. Vitamin B-6 deficiency is
considered rare in human populations, although marginal deficiency
may occur more frequently. Deficiency of vitamin B-6 produces
profound skin and neurological changes, such as peripheral 
neuropathy. Vitamin B-6 is often co-administered with Isoniazid (a
tuberculosis treatment) to reduce drug-related toxicities. Other uses
of Vitamin B-6 (some of which are controversial) include: as a
stimulant of hematopoiesis in patients with siderblastic anemia, as a
treatment for iron-storage disease, as a treatment for schizophrenia,
and as ma treatment to reduce the incidence of seizures in 
alcoholics. 

Vitamin B-6 and Immunity

Little is known about this vitamin's role in immunity or its mechanism
of action, although it appears to play a significant role. Animal
studies suggest that B-6 deficiency has a range of effects on cell
mediated immunity. Delayed-type hypersensitivity reactions to
tuberculin antigen are decreased in guinea pigs fed a B-6 deficient
diet.[24] Lymphocyte proliferation and cytotoxicity are reduced in
mice after five weeks on a B-6 deficient diet.[25, 26] Vitamin B-6 
deficiency in animals may also lead to lymphoid organ atrophy and
impaired thymic function[27], reduced T lymphocytes numbers and
function[28], and defective lymphocyte maturation.[29] Vitamin B-6
deficiency can also lead to impaired antibody production and fewer
antibody-producing cells in animals, according to various
studies.[30, 31, 32]

Few human studies address the issue of vitamin B-6 and immunity, and
those that have examined the question demonstrate no consistent
direction of effect. Two studies of vitamin B6 deficiency in humans
show that it may slightly impair antibody production[33] or leave it
unchanged.[34]

Vitamin B-6 and AIDS

There has been little research directed at Vitamin B-6 and AIDS. No
study has shown that Vitamin B-6 supplements delay disease
progression or improve survival. One study examined Vitamin B-6
levels in a group of HIV-infected people and that 35 percent of
subjects had overt deficiency and an additional 18 percent had
marginal deficiency. The authors suggest that CD4 cell counts were
lower in patients with reduced vitamin B-6. The authors also suggest
that vitamin B-6 intake was inadequate in these subjects, based on
food intake surveys. However, the diagnosis of vitamin B-6 serum
levels is difficult and may be affected by the APR. Food intake
surveys are also not considered a reliable method for diagnosing
vitamin deficiency. 

Vitamin B-6 may be reduced when tumor necrosis factor (an inflammatory
cytokine) is increased, according to a study of rheumatoid arthritis
patients.[35, 36] Furthermore, Vitamin B-6 is stored in muscle and
deficiency may be related to decreased lean body weight. 

Vitamin B-12 and Folate 

Vitamin B-12 and folate are separate vitamins, although they have
similar biological roles and work together in vivo. Folate is
critical to the synthesis of RNA and DNA. The main biological effect
of Vitamin B-12 is probably on folate metabolism. Folate is found in
most foods, although its deficiency is common in the developed world,
affecting an estimated 8 to 10 percent of the population. Vitamin
B-12 is produced mainly by bacteria which live in the human gut, 
although it is also found in meat. Vitamin B-12 deficiency is
considered rare, except in some strict vegetarians who endure 20 to
30 years of inadequate intake, suggesting there are considerable body
stores of the vitamin. Most Vitamin B-12 deficiency is thought to
result from altered intestinal flora and malabsorption. Folate and
Vitamin B-12 deficiency result in clinically similar syndromes,
producing anemia and neurologic symptoms. 

Folate utilization can be impaired (thus producing a functional
deficiency despite adequate intake) in the context of Vitamin B-12,
methionine (an amino acid) or zinc deficiencies. Some drug therapy
can also cause functional folate deficiency Folate deficiency can
also cause neural tube defects (a birth defect in children born to
mothers who consume inadequate amounts of the nutrient).

Folate/B-12 and Immunity

Very little published information addresses the role of folate and
Vitamin B-12 in immunity. Folate deficiency causes anergy to DNCB in
pregnant women and impaired lymphocyte proliferation.[37] Folate
deficiency causes lymphoid organ atrophy, reduced T-cell numbers, and
lymphocyte proliferation in laboratory animals.[38] Vitamin B-12
deficiency, but not folate, reduces phagocytosis and bacterial
killing by neutrophils in humans.[39]

Folate and Vitamin B-12 in AIDS

Although these two vitamins are not considered to play a key role in
immunity, have received considerable attention in HIV disease because
of vitamin B-12's potential role in neurologic disease. Numerous
studies detected low serum levels of the nutrient in this
population.[40, 41, 42] The mechanism of these deficiencies is not
known, although gastrin was elevated in one study population - a sign
of defective B-12 absorption. Vitamin B-12 deficiency may be an
important cause of neurological disorders and anemia in people with 
HIV, leading some physicians to offer periodic B-12 injections to
their patients. The clinical efficacy of this intervention remains
unproved, however. Folate levels may be increased in HIV-infection,
according to several studies. One study suggested that IV-drug users
may have reduced folate levels because of poor access to fresh fruits
and vegetables - key sources of folate. Gay men, the authors
speculate, probably do not have reduced folate because of better
access to fresh foods, although they present no evidence to support 
this hypothesis.[43, 44, 45]

Vitamin C

Vitamin C (ascorbic acid) is found in many foods, including citrus
fruits, green vegetables, berries, and organ meats. Most animal and
plant species do not need to consume Vitamin C in their diet as they
are able to produce sufficient quantities naturally. Humans and
guinea pigs are the only animals that can not produce Vitamin C
naturally and thus must consume it. Vitamin C is critical to electron
transport, collagen synthesis, and various metabolic processes. The 
deficiency of Vitamin C produces connective tissue disorders, impaired
wound healing, bleeding gums, and other serious symptoms. The
deficiency of Vitamin C is called scurvy, the bane of sailors for
hundreds of years. 

Unlike other vitamins, marginal Vitamin C deficiency is somewhat
better characterized. It may produce fatigue, muscle weakness, and
impaired wound healing. 

Vitamin C and Immunity

Vitamin C supplementation has not been shown to delay progression or 
improve survival in people with HIV. 

Vitamin C deficiency does not impair lymphocute proliferation or CD4
and CD8 levels in humans.[46] In guinea pigs, Vitamin C deficiency
impairs tuberculin skin reactions, cell-mediated cytotoxicity, and
decreases the bactericidal capacity of neutrophils.[47, 48] Vitamin C
can induce interferon production in vitro.[49] Animal and human
studies demonstrate conflicting results on Vitamin C's impact on
antibody formation.[50, 51, 52, 53, 54] Several in vitro and animal 
studies indicate, however, that Vitamin C may play a more significant
role in cellular immunity.[55, 56]

Vitamin C and Viral Diseases

Vitamin C has been proposed an antiviral agent for several diseases, 
beginning with a report from 1935 on the nutrient's ability to
inactivate polio virus in vitro.[57] Vitamin C was also able to
inactivate other viruses in vitro, including herpes simplex, rabies,
and tobacco mosaic virus. Not surprisingly, massive doses of Vitamin
C were used as a polio treatment, although they were ineffective. 

Vitamin C was also proposed as a treatment for the common cold. One 
investigator claimed that regular doses of Vitamin C would reduce the
incidence of the common cold.[58] This claim was later disproved.[59,
60, 61] Vitamin C was also proposed as a cancer treatment, by the
same investigator who suggested it could prevent colds. These results
remain controversial, although studies which claim a beneficial
effect suffer from serious methodological flaws. A study conducted by
the Mayo Clinic found that Vitamin C was not beneficial as a cancer
treatment. In fact, those who received Vitamin C had shorter
survival, but not to a statistically significant level.[62]

Vitamin C and AIDS

It should come as no surprise, perhaps, that massive doses of Vitamin
C are now proposed as an AIDS treatment. There have been no clinical
studies designed to address this question. Claims for the efficacy of
Vitamin C in AIDS are based entirely on reports of the nutrient's
ability to inactivate HIV in vitro.

Vitamin Discovery

Christian Eijkman, a Dutch physician, was the first to isolate a
vitamin, although initially he did not understand his discovery. An
advocate of the recently proposed germ theory of disease and a
student of Robert Koch, the great German bacteriologist, Eijkman
first believed that he had found an "antidote" to the "microbe" that
causes beri-beri disease. Eijkman later realized that he had, in
fact, discovered what would be known as thiamin (Vitamin B-1), the 
deficiency of which causes beri-beri. In 1929 Eijkman received the
Nobel Prize for his discovery. 

The discovery of thiamin sparked a world-wide effort that lead to
further discovery of other vitamins. Casimir Funk, a Polish
biochemist, is credited as the first to coin the term vitamin after
he discovered that thiamin's chemical structure contains an ammonia
molecule. He merged two words - "vital" and "amine" (the chemical
suffix for ammonia) - to create the term vitamin. By 1948, all
thirteen presently-recognized vitamins had been discovered.

Table I: Core Foods For Vitamins

 Vitamin A
 Liver 
 Red peppers 
 Spinach
 Carrots
 Eggs
 Kale 
 Butter
 Margarine*
 Milk* 

 Vitamin C
 Tomatoes
 Potatoes
 Most fruits and vegetables

 Vitamin B-6
 Meat
 Cabbage
 Potatoes
 Liver
 Beans
 Whole grains
 Peanuts
 Soybeans
 Fish
 Milk

 Vitamin B-12
 Liver 
 Fish 
 Eggs
 Milk

 Vitamin D
 Milk*
 Margarine*
 Chicken skin
 Liver
 Fatty fish, such as herring
 Egg Yolk
 Thiamin
 Meats
 Potatoes
 Liver
 Whole grains
 Fish
 Legumes
 Biotin
 Liver 
 Egg yolk
 Cauliflower
 Kidney
 Peanuts
 Soybeans
 Wheat germ
 Oatmeal
 Carrots

 Vitamin E
 Vegetable oils
 Riboflavin
 Eggs
 Liver
 Meat
 Fish
 Asparagus
 Milk
 Whole grains
 Pantothenic acid
 Liver
 Milk
 Meats
 Eggs
 Fish
 Whole grains
 Legumes

 Vitamin K
 Broccoli
 Lettuce
 Cauliflower
 Cabbage
 Brussels sprouts
 Turnip greens
 Liver 
 Spinach
 Asparagus
 Niacin
 Meats
 Eggs
 Fish
 Whole grains
 Legumes
 Milk
 Folate
 Tomatoes
 Beets
 Potatoes
 Wheat germ
 Cabbage
 Eggs
 Meats
 Spinach
 Asparagus
 Liver
 Soybeans
 Whole grains
 Milk

 * High Vitamin Content is due to fortification

 Adapted from The Vitamins. by Gerald F. Coombs Jr. New York. The Academic 
Press, 1992.

Table II: Vitamin Toxicities

Vitamin A: Vitamin A may be the most toxic vitamin. Its threshold for
safe intake is quite small compared to other vitamins. Toxicities
have been reported at levels as low as 25 times the RDA. Most
toxicities appear to occur after consumption of 25,000 to 50,000 IU
per day for several months. Birth defects have been noted when
pregnant women consume more than 25,000 IU per day. Signs of vitamin
A toxicity include: loss of appetite, weight loss, bone 
malformations, spontaneous fractures, and internal bleeding. These
toxicities can be reversed when the vitamin is discontinued.

Vitamin D: Vitamin D is also a very toxic vitamin. Adverse reactions
have been reported after single overdoses as low as 50 times the RDA.
Overzealous fortification of infant formula with vitamin D in Britain
in the 1950s resulted in Vitamin D toxicities in many children.
Vitamin D toxicity causes bone lesions. 

Vitamin E: There is little data, but the toxic potential of this
vitamin appears very low. Intake over 100-times the RDA for several
months results in no toxicities. 

Vitamin K: This vitamin does not appear toxic at any dose in humans
when given orally. Intravenous administration of Vitamin K at doses
of 2 to 8mg/kg is lethal in horses, however.

Vitamin C: This vitamin is moderately toxic. Intake at 20 to 80 times
the RDA produces gastrointestinal disturbances and diarrhea. People
with a history of calcium oxalate kidney stones should consult a
physician before taking high doses of this vitamin.

Thiamin: Thiamin has a low toxicity when given orally. Intravenous
doses at 100 to 200 times the RDA has caused intoxication in humans,
involving headache, convulsions, muscular weakness, paralysis, and
cardiac arrhythmias. 

Riboflavin: No riboflavin toxicities have been reported in humans at
any dose. 

Niacin: The toxicity of niacin may be related to the chemical form in
which it is consumed. Nicotinic acid can cause itching, nausea,
vasodilatation, and vomiting in humans at doses of 2 to 4g/day.
Nicotinamide only rarely produces these toxicities and is the
preferred medical form of the vitamin. 

Vitamin B-6: This vitamin causes toxicities only at high doses given
over long periods. Doses of 500mg to 6g/day can cause reversible
neuropathies in humans. 

Pantothenic acid: No toxicities have been reported with pantothenic
acid in humans. When given intravenously, this vitamin can be lethal
in rats at doses of 1g/kg.

Biotin: No toxicities have been reported in humans at any dose. 

Folate: High doses of folate in humans are associated with reduced
zinc absorption. No other toxicities have been established for any
dose.  Vitamin B-12: This vitamin is considered non-toxic, but rare
allergic reactions have been reported in humans.

1. Roughly speaking the RDA are determined in the following way:
Individual variation in vitamin and mineral requirements is assumed
to follow a normal statistical distribution. Mean observed (or, in
some cases, estimated) individual vitamin and mineral requirements
have been established and refined over the years by numerous studies.
The mean observed requirement plus twice the standard deviation
yields an RDA level that has a 97.5 percent probability of meeting an
individual's unique requirements. Accordingly, there is also a 2.5 
percent probability that the RDA is inadequate for any one individual.

2. Bang FB, et al. American Journal of Pathology. 1975;79:417-24.

3. []avis CY, et al. Poultry Science. 1989;68:136-44. 

4. Darip MD, et al. Proceedings of the Society of Experimental Biology and 
Medicine. 1979;161:600-4. 

5. Friedman A, et al. Journal of Nutrition. 1991;121:395-400. 

6. Ongsakul M, et al. Proceedings of the Society of Experimental Biology and 
Medicine. 1985;178:204-8.

7. []eutskaya ZK, et al. Acta Biochimie et Biophysique . 1977;475:207-216.

8. Yamamoto M, et al. Nutrition Research. 1988;8:529-38. 

9. Rahmathullah L, et al. New England Journal of Medicine. 1990;323:929-35.

10. Keusch GT. New England Journal of Medicine. 1990;323:985-6.

11. Pinnock C, et al. Australian Paediatric Journal. 1986;22:95-9. 

12. Sommer A, et al. The Lancet. 1986;1:1169-73.

13. Hussey GD, et al. New England Journal of Medicine. 1990;323;160-4.

14. Olson J. Factors Affecting the Bioavailability and Metabolism of VITAMIN 
A and its Precursors. In: Santos W, et al. Nutritional Biochemistry and 
Pathology. 1980. Plenum Press. New York. 

15. Markowitz LE, et al. Journal of Tropical Pediatrics. 1989;35:109-12.

16. Campos FACS, et al. American Journal of Clinical Nutrition. 1987;46:91-94. 

17. Usha A, et al. Journal of Pediatric Gastroenterology and Nutrition. 
1991;13:168-75.

18. Sommer A. Annals of the New York Academy of Sciences. 1990;587:17-21. 

19. Semba RD, et al. Archives of Internal Medicine. 1993;153:2149-54.

20. Karter DL , et al. Abstract PoB 3698. Eighth International AIDS Conference, 
Amsterdam. 1992.

21. Beach RS, et al. AIDS. 1992;6:701-8. 

22. Poli G, et al. Proceedings of the National Academy of Sciences. 
1992;89:2689-93.

23. Turpin JA, et al. Journal of Immunology. 1992;148:2539-46. 
24. Axelrod AE, et al. Journal of Nutrition. 1963;79:161-7.
25. Sergeev AV, et al. Cellular Immunology. 1978;38:187-92.

26. []a C, et al. Cellular Immunology. 1984;85:318-29. 

27. Stoerk HC, et al. Journal of Experimental Medicine. 1947;85:365-71.

28. Willis-Carr JI, et al. Journal of Immunology. 1978;120:1153-9. 

29. Chandra RK, et al. Vitamin B-6 Modulation of Immunity and Infection. In: 
Vitamin B-6: Its Role in Health and Disease. New York: Alan R. Liss, 1985: 
163-75.

30. Axelrod AE, et al. Proceeding of the Society of Experimental Biology and 
Medcine. 1947;66:137-40.

31. Chandra RK, et al. Annals of the New York Academy of Sciences. 
1990;585:404-23.

32. []umar M, et al. Journal of Nutrition. 1968;96:53-9.

33. []odges RE, et al. American Journal of Clinical Nutrtion. 1962;11:180-6. 

34. []ayne L, et al. Archives of Internal Medicine. 1958;101:143-55. 

35. Roubenoff R, et al. Journal of Rheumatology. 1992;19:1505-10.

36. Rall LC, et al. FASEB Journal. 1993;7:A728.

37. Gross RL, et al. American Journal of Clinical Nutrition. 1975;28:225-32.

38. IGershwin ME, et al. Nutrition and Immunity. 1985. Academic Press, New 
York. 228-58. 

39. Ibid

40. Burkes RL, et al. European Journal of Hematology. 1987;38:141-7.

41. Harriman GR, et al. Archives of Internal Medicine. 1989;149:2039-41. 

42. []remacha A. European Journal of Hematology. 1989;42:506. (letter)

43. Beach Rs, et al. Journal of the American Medical Association. 1988. 
259:519.

44. Herbert V, et al. Clinical Research. 1990. 38:361A.

45. Herbert V, et al. FASEB Journal. (abstract). 1989. 37:594A.

46. Kay NE, et al. American Journal of Clinical Nutrition. 1982;36:127-30. 

47. Goldschmidt MC, et al. International Journal of Vitamin and Nutrition 
Research. 1988;58:326-334. 

48. Anthony LE, et al. American Journal of Clinical Nutrition. 1979;32:1691-8. 

49. Siegel BV. International Journal of Vitamin and Nutrition Research. 
1979;49(Supp 19):201-3. 

50. Vallance S. British Medical Journal. 1977;2:437-8.

51. Anderson R, et al. South African Medical Journal. 1980;58:974-7. 

52. Prinz W, et al. International Journal of Vitamin and Nurtrition Research. 
1977;47:248-57. 

53. Panush RS, et al. Interbnational Journal of Viotamin and Nutrition 
Research. 1979;49(Supp 19):179-99. 

54. Kennes B, et al. Gerontology. 1983;29:305-10. 

55. Delafuente JC, et al. International Journal of Vitamin and Nutrition 
Research. 1980;5:44-51.

56. Mueller PS, et al. Journal of Experimental Medicine. 1962;115:329-338. 

57. Jungeblut CW. Journal of Experimental Medicine. 1935;62:517-21. 

58. Pauling L. Vitamin C, the Common Cold and the Flu. 1976. Freeman Press: 
San Francisco. 

59. Beaton GH, et al. Canadian Medical Association Journal. 1971;105:355-7. 

60. Anderson TW, et al. Canadian Medical Association Journal. 
1972;107:503-8. 

61. Karlowski TR, et al. Journal of the American Medical Association. 
1975;231:1038-42. 

62. Creagan ET, et al. New England Journal of Medicine. 1979. 301:687-90.


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 ^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^

Traditional Chinese Medicine
 By Jason Heyman

The little research that has been done on traditional Chinese medicine
for the treatment of HIV and AIDS shows promise in a number of areas
that Western medicine has been unsuccessful in treating. A
combination of different medical approaches may be the most effective
way to treat conditions, such as AIDS, that no one system has been
able to cure.

Western, or allopathic, medicine tends to view the body as a war zone
where battles against invading organisms are fought, and won or lost.
Therapeutic approaches are usually based on our intellectual ability
to understand the nature of the battle being fought, and to employ an
effective arsenal of weapons. 

Many diseases have been effectively cured or subdued in this fashion,
but some illnesses have eluded Western medical treatment, including
most viral infections (such as HIV), genetic defects, and cancer. In
the case of AIDS, some Western treatments for opportunistic
infections are effective, such as the use of antibiotics in fighting
PCP, while treatments for Kaposi's Sarcoma have generally failed. 

Different cultures' theories about the cause, pathogenesis, and
outcome of disease, form the foundation for their medical practices.
Western medicine relies upon the belief that there is a physical
cause for most medical problems, such as a bacterium, virus, or
genetic trait, and that destroying or neutralizing that agent will
return a patient back to a state of health. One aspect that most 
non-Western cultures share is a belief in holism - the idea that the
physical body is inseparable from the mind, emotions and spirit (or
soul). Differing views of death also affect whether a culture chooses
to use medicine to fight death, or uses medicine to make a limited
life span as comfortable as possible.

The prognosis of a disease is affected by these different
philosophical approaches, as are its actual course and outcome. The
results of a well known study of women with breast cancer at Stanford
University depicts one aspect of holism - that emotional support has
a direct impact on health. In this study women who were involved in a
support group with other patients benefited from the emotional
support of the other women and had an increased life span of two 
years.[1]

Traditional Chinese Medicine

In traditional Chinese medicine (TCM), health is understood to be a
balance between a variety of constantly changing variables. An
imbalance is usually seen as the result of a variety of factors. This
methodology is explained in the book AIDS and Chinese Medicine:

"Eight principles are used to summarize clinical symptoms: yin or
yang, exterior or interior, hot or cold, and deficiency or excess. In
addition to these principles, there are analytical rules: three
etiologies (external, internal, and neither external or internal
factors), differential diagnosis by analysis of the state of five 
solid organs, and analysis and differentiation of the diseases
according to the state of vital energy (qi) and blood."

"First and foremost, TCM emphasizes treatments which enhance the
body's natural immunities so that it may more effectively resist
disease. Specifically, the fundamental principles of TCM for the
treatment of infectious diseases are: fu zheng (supporting the body's
natural order, i.e. enhancing immunity), and quxie (eliminating
external evil, i.e. reducing the potency of the pathogen)."[2]
Treatment consists of a tea distilled from a combination of medicinal
herbs, and acupuncture, but may include breathing exercises (qi
gong), and massage. Acupuncture and qi gong are believed to increase
the circulation of qi, and acupuncture is often used to control pain.

A study of acupuncture for the treatment of HIV-related peripheral
neuropathy showed a small improvement in "quantitative sensory
testing" (which is a test of sensitivity to applied stimulation in
the hands and feet). There was also improvement in quality of life as
assessed by self-administered questionnaires.[3] These findings are
preliminary, but they do attempt to study the effects of a treatment
that is difficult to measure by Western medical standards. 

Chinese Herbs

Some of the herbs most commonly used in Chinese medicine for the
treatment of immune disorders are, astragalus, Eleutherococcus
senticosus, and Panax notoginseng. The mode of action of these herbs
in unknown, and there has been some speculation, as a result of in
vitro studies, that they could be dangerous for people with HIV and
AIDS.[4]

Misha Cohen, L.Ac., OMD, director of the Quan Yin Chinese Herbal
Clinic, in San Francisco, explained that the combination of herbs
employed in traditional Chinese medicine has a balancing effect on
the immune system that is not apparent in laboratory studies, but can
be seen in a clinical setting. She cautioned that herbs can be very
potent - as dangerous, in some cases, as any pharmaceutical drug -
and anybody who is considering using Chinese herbal medicine should
see a qualified Chinese herbalist.[5]

The mechanism of action of most herbs is unknown. According to Subhuti
Dharmananda, of the Institute for Traditional Medicine, in Seattle,
Washington, "some of the herbs which are used to treat depressed
immunity also appear to successfully treat auto-immune diseases
(which in Western medicine are treated by inhibiting rather than
enhancing immune function). This suggests that the complex herbal
ingredients effectively modulate or regulate the immune functions
instead of simply stimulating them."[6]

Herbal formulas

To counteract unwanted side effects, and to increase their efficacy,
herbs are used in combinations from formulas that are often centuries
old. Traditionally the whole herbs are cooked slowly and the
resulting decoction is drunk as a tea. This process can be
time-consuming and the tea is often unpleasant to drink. In the past
few years practitioners have developed standardized herbal formulas
in the form of pills that are easier to use. 

In 1986, Cohen and Dharmananda created one of the first herbal
formulas for AIDS. This compound, known as Astra Eight, was based on
a traditional Chinese formula that is used to treat immune deficiency
in people undergoing chemotherapy for cancer.

In 1988 researchers systematically tested Chinese herbs for antiviral
activity against HIV in vitro.[7] This work lent some credibility to
the herbal compounds since many of the herbs being employed were
found to have inhibitory activity against HIV and other viruses.
Eleven herbs were found to be active against HIV. The three most
active were Viola Yedoensis, Arctium lappa, and Andrographis
paniculata.

One of the herbs found to have anti-HIV qualities, Hypericum
japonicum, has been used as an alternative AIDS treatment in an
extracted form known as hypericin. Other plants from Chinese medicine
have been used in this manner, such as Trichosanthes Kirilowii
(compound Q), Shiitake mushroom (lentinan), and Momordica charantia
(bitter melon). 

In the past few years two particular formulas have become popular in
the treatment of HIV and AIDS, these are Enhance (created by Cohen)
and Composition A (created by Dharmananda). There are approximately
thirty ingredients in these compounds, including; Ganoderma, Isatis,
Astragalus, Ginseng, and Licorice. The main difference between these
two formulas is that Composition A contains deer antler and Enhance
does not. Deer antler is understood in Chinese medicine to activate
bone marrow, and has been shown in a laboratory study to have
anti-inflammatory qualities.[8]

There is some disagreement among traditional Chinese practitioners as
to whether these herbal formulas work as well as the traditional
cooked herbs, claiming that the strength of Chinese medicine lies in
its ability to treat each patient as an individual.[9] Unlike cooked
herbs, herbal formulas do not vary from person to person. Instead,
practitioners prescribe a combination of formulas to suit a patient's
needs. 

Research on Herbal Formulas

Over the years a number of observational studies have been done on the
effects of Chinese herbal formulas on patients with HIV and AIDS.
These studies show large improvements in symptoms, but since they are
unblinded and without control groups, the results have to be viewed
with some skepticism.[10, 11, 12, 13]

San Francisco General Hospital recently concluded the first
double-blinded, controlled clinical trial of a Chinese herbal
compound for the treatment for AIDS at a major research
institution.[14] Cohen formulated the compound and collaborated with
Western-trained researchers in this ground-breaking study.  The
formula was tested against a placebo which had been manufactured to 
look and taste the same. Thirty subjects were recruited, with t-helper
counts between 200 to 500, who were experiencing symptoms but did not
have an AIDS diagnosis. Participants took 28 pills per day for a
period of twelve weeks.  The pilot study showed that there was a
statistically significant improvement in the areas of "life
satisfaction", fatigue, gastrointestinal symptoms, and neurological
symptoms, all of which were measured by standardized questionnaires.
These four outcome variables are all areas that Western medicine has
been particularly unsuccessful in treating. 

The small sample size limits the scope of these findings. But if
future research, undertaken on a larger scale, can reproduce these
results than they could have a serious impact on the standard of care
in AIDS treatment. This kind of cooperation, between practitioners of
traditional Chinese medicine and Western-trained medical personnel,
could in itself lead to significant advances. 

1. Spiegel D et al. Effect of psychosocial treatment on survival of
patients with metastatic breast cancer. The Lancet. October 14, 1989;
pages 888-891.

2. Zhang Q, Hsu H. AIDS and Chinese Medicine, Applications of the Oldest 
Medicine to the Newest Disease, 1990. OHAI Press.

3. Tosches W et al. A pilot study of acupuncture for the symptomatic
treatment of HIV associated peripheral neuropathy. Community Research
Initiative of New England. Published in the proceedings of; HIV, AIDS
and Chinese Medicine, First International Conference. San Francisco
State University, San Francisco, CA. June 18-20, 1993.

4. Caulfield C, Goldberg B. Chinese Herbs for HIV: A Critical Review.
The San Francisco Sentinel, September 15, 1993. Pages 22-23.

5. Personal Communication, September 27, 1993.

6. Dharmananda S. "Commonly asked questions about Chinese herbal 
therapies for HIV, some answers from Institute for Traditional Medicine." 
Institute for Traditional Medicine brochure, June 1989. 

7. Chang R, Yeung H. Inhibition of growth of Human Immunodeficiency
Virus in vitro by crude extracts of Chinese medicinal herbs.
Antiviral Research #9, 1988, pages 163-176.

8. Zhang Z, et al. Purification and partial characterization of
anti-inflammatory peptide from pilose antler of Cervus nippon
Temminck. Yao Hsueh Hsueh Pao Acta Pharmaceutica Sinica, 27(5),1992,
pages 321-324.

9. Weibo L. Oral presentation at the Satellite workshop; "Evaluation
of Case Studies of Alternative Treatments." IX International
Conference on AIDS in Berlin, June 6-11,1993.

10. Young M. Chinese herbal therapies and HIV infection, a clinical
report. Published in the proceedings of; HIV, AIDS and Chinese
Medicine, First International Conference. San Francisco State
University, San Francisco, CA. June 18-20, 1993.

11. James J. Chinese fu zheng therapy: the Immune Enhancement Project. 
AIDS Treatment News #25, February 13, 1987.

12. Hawkins M et al. Use of a Chinese herbal composition for the
treatment of Human Immunodeficiency Virus - a descriptive study.
Published in the proceedings of; HIV, AIDS and Chinese Medicine,
First International Conference. San Francisco State University, San
Francisco, CA. June 18-20, 1993.

13. The San Francisco AIDS Alternative Healing Project. Quan Yin 
Publications, San Francisco, CA. 1987.

14. Burack J, Cohen M, Hahn J, Abrams D. Chinese herbal treatment of
HIV-associated symptoms. Abstract PoB 29-2191 from the IX
International Conference on AIDS in Berlin, June 6-11, 1993.


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Antioxidants, Oxidative Stress, and NAC
 by Carole Lemens and Craig Sterrit

Oxidative stress has emerged in recent years as a suspected component
in the pathogenesis of HIV disease. Increasing numbers of researchers
agree that even in the earliest stages of infection, a deleterious
reductive-oxidative (redox) imbalance may occur, This means that
increased damage causing reactive oxygen intermediates (also called
"free radicals") are generated at the same time that stores of
naturally occurring antioxidant reducing agents are depleted. The
possible result is the uncontrolled presence of oxygen-containing
molecules which may cause damage to cell membranes, proteins and
nucleic acids, and alterations in the intra- and inter-cellular
environments. The net effect of this damage has been termed oxidative
stress. 

Free radicals are oxygen atoms (or oxygen containing molecules) that
are produced normally as intermediaries in cellular processes and
respiration, and in the degradation of fatty acids. Free radicals are
also generated by phagocytes (a type of immune cell) in the
destruction of bacteria and virally infected cells, which leads some
to speculate that increased oxidative stress occurs during
inflammatory immune responses. 

Antioxidants are compounds with a chemical affinity for free radicals.
They exist in abundance and bond with free radicals before they can
cause damage. Antioxidants are of five classes: enzymes, such s
catalases, peroxidases, and superoxide dismustase (SOD); peptides,
such as glutathione; phenolic compounds. like Vitamin E and plant
flavonoids; nitrogen compounds. which includes various amino acids;
and carotenoids, most notably beta-carotene. 

Other agents may have antioxidant effects through replenishing mechanisms - 
Vitamin C, for instance, helps to recycle Vitamin E, and NAC (N-acetyl 
cysteine) provides an important component of glutathione. 

Low levels of free radicals are necessary for a number of important 
physiological functions including the inflammatory response, cell
division, and white blood cell action against bacterial infection.
Thus the importance of maintaining a system of checks and balances
between antioxidants and free radicals and their compounds, where the
balance is weighted on the side of antioxidants. 

When the balance between free radicals and antioxidant supply is
tipped, resulting oxidative stress can cause many problems -- either
on its own or, in the case of HIV, increased viral replication. The
most interesting evidence in HIV suggests that oxidative increases
the HIV activation, which, in turn, increases free radical production
and oxidative stress. But increased free radical production has been
found in serious diseases, including cancer, HIV, and other viral
diseases, and has been termed by a causative factor for disease and
an effect of underlying pathology. 

Limited scientific evidence links low levels of antioxidants (in
particular vitamins C and E) with higher incidence of heart disease
and cancer. There is no scientific evidence which proves that
antioxidants improve disease progression or survival in people with
HIV. Part of the confusion stems from the dilemma: are increased free
radicals a cause or effect of disease? There is no solid evidence in
either direction. 

This article will focus on the function of glutathione (GSH), and the
theory and evidence to date of the role of the GSH replenishing drugs
NAC (N-Acetyl Cysteine) and Procysteine (OTC) in HIV disease. 

NAC and Procysteine 

NAC is a derivative of cysteine, an amino acid, which is essential for
the synthesis of GSH in the body. It has been used as a possible
treatment for HIV infection for over three years. In the U.S. it is
available as the prescription aerosolized drug Mucomyst by Bristol
Laboratories, a division of Bristol-Myers and is used to treat
acetaminophen (Tylenol) overdose and chronic bronchitis. In Europe
where it has been used orally for decades it is marketed under the
trade name of Fluimucil by Italy's Zambon group. The oral European 
version of NAC is available at buyers' clubs in the United States.

Procysteine (OTC), a precursor of cysteine, is manufactured by Clintec
Nutrition and is currently in use in phase II clinical trials for HIV
infection. It is not commercially available. 

The rationale for the use of NAC in HIV treatment is based on evidence
from in vitro studies that cells deficient in GSH are particularly
sensitive to inflammatory cytokines (tumor necrosis factor alpha).
Elevated levels of TNF are known to activate and increase
replication. That is when TNF stimulates the nuclear transcription
factor kB (NF-kB) in HIV-infected cells, virus transcription and
replication is greatly increased. By increasing the levels of
intracellular GSH, proponents of NAC therapy hope to offset
TNF-mediated HIV replication.  GSH is present in almost all human
tissues. It is critical for a number of important cellular functions.
Of primary importance, however, is its vital role as the principal
intracellular defense against oxidation by free radicals and their 
compounds. In their 1992 review article Staal et al reported that
"adequate levels of GSH are required for mixed lymphocyte reactions,
T-cell proliferation, T and B cell differentiation, cytotoxic T-cell
activity, and natural killer cell activity. Decreasing GSH by 10 to
40 percent can inhibit completely T-cell activation in vitro. Thus,
an intracellular GSH deficiency in lymphocytes has profound effects
on immune functions."

Abnormally low levels of GSH have been found in asymptomatic
HIV-infected individuals. It has also been shown that concentrations
of GSH within peripheral blood mononuclear cells (PBMCs) subsets (CD4
and CD8 T cells, B cells, and monocytes) within healthy controls have
two distinct types of CD4 and CD8 cells containing high and low
levels of GSH. Although the levels vary from individual to
individual, the ratio of high GSH content to low GSH content CD4+ and
CD8 cells remain constant. In asymptomatic HIV-infected individuals 
high GSH content T cells appear selectively depleted.

Droge reported that both humans with HIV infection and rhesus macaques
with SIV infection have increased plasma glutamate levels, which even
when minimally elevated cause a substantial decrease of intracellular
cysteine levels (a major component of GSH). He noted that in clinical
studies these levels in both HIV infected and uninfected controls
corresponded to lymphocyte reactivity and CD4+ but not CD8 T
lymphocyte counts. He reported further that the level of cellular
cysteine affects both the "intracellular glutathione level and IL-2
dependent proliferation of T cells." He thus concluded "that the
cysteine deficiency of HIV persons is, therefore, possibly 
responsible not only for the cellular dysfunction but also for the
over- expression of tumor necrosis factor alpha, interleukin-2
receptor alpha chain, and B2-microglobulin."

Staal et al, among others, advocate for the use of NAC as a
therapeutic agent in AIDS. The reasons they state: "NAC has
antiretroviral effects in vitro, low toxicity in vivo, a long history
of use in patients, can be given orally in a palatable form and is
inexpensive."

Clinical Studies

The paucity of clinical trials is in stark contrast to the numbers of
PWAs who take NAC and the sweeping recommendations drawn from in
vitro studies. 

Quay et al reported that oral doses of NAC can temporarily increase
levels of cysteine and glutathione in some patients with HIV disease.
The objective of the trial was to examine the mechanisms underlying
the depletion of glutathione at different stages of HIV infection and
the possibility of correcting the deficiency of cysteine and
glutathione by the oral administration of NAC.  The authors observed
a decrease in both glutathione and cysteine in HIV-infected subjects.
GSH depletion became more marked with disease progression.  The
observation of cysteine depletion led them to conclude that 
glutathione deficiency is the result of cysteine deficiency and not
of increased consumption of glutathione by oxidative stress.

Nine male patients at various stages of HIV infection were studied.
Six uninfected volunteers served as controls. Blood was taken before
and at several intervals after the oral administration of NAC at
30mg/kg body weight. Three to four-fold increases in both plasma and
PBMC levels of cysteine were seen in all subjects, yet intracellular
glutathione increased moderately only in subjects at the least severe
stages of HIV infection. The authors felt that "since the rate of
glutathione synthesis in PBMC is rather slow, a longer exposure to 
normal concentrations of cysteine may be required for a biologically 
meaningful increase in intracellular glutathione." The example of one
patient who took 600mg of NAC three times daily resulted in a
two-fold increase of the concentration of glutathione in PBMC.
However, they stated that "whether a sustained increase in
intracellular cysteine affects the function of PBMC or viral
replication of HIV in the long term remains to be determined." 

It was further observed that levels of plasma concentration of the
drug shown to be effective in inhibiting viral replication in vitro
were "more than three orders lower" even after ingestion of large
doses of NAC.

They conclude that "our results indicate that large doses of NAC
should be administered repeatedly to achieve a sustained increase in
intracellular GSH." and that "further studies should determine
whether pharmacological modulation of the GSH status alters the
natural history of HIV infection." The authors suggest that a
tolerable daily dose for prolonged administration would be 
approximately 2 grams.

Side effects of oral administration of NAC are minimal, and are
limited to nausea, vomiting or diarrhea and, rarely, bronchospasms in
patients with asthma.

The Herzenberg Laboratory of Stanford University is now recruiting for
an eight week trial of NAC. Its objective is to learn definitively
whether oral NAC can replenish glutathione levels inside T cells of
people with HIV. Participants must be HIV positive with a CD4 count
of 500 or less. They will be assigned to take a total of 9600mg of
NAC per day or placebo. For more information, call Debra Fial R.N.,
or Greg Dubs, Ph.D., at 415/863-8090.

A partially randomized placebo controlled, phase I trial of the oral
form of Procysteine (OTC) in 36 asymptomatic patients with CD4 counts
over 400 were enrolled in a one month safety and pharmacokinetics and
dose ranging study. Participants were randomized to receive OTC 500,
1500 or 3000mg three times daily or placebo. Skowron et al reported
no serious drug related toxicities. Mild gastric upset was seen at
the highest dose during chronic dosing. The researchers noted that
changes in CD4 and CD8 ratio and in CD4 percentages were greater in
the treated groups in a dose dependent way; however, variability and
the small number of patients in each group precluded statistical 
significance. Weight gain and a reduction in beta-2 microglobulin was
seen in some patients on OTC; no significant changes in viral load
were seen.

A Phase II/III double blind placebo controlled safety and efficacy
study of oral OTC study is currently under way involving 168 patients
with CD4 counts between 50 and 300 if symptomatic and between 50 and
200 if asymptomatic were randomized to receive oral OTC 1500mg,
3000mg, or placebo three times a day for one year. It would appear
that this study may close due to restriction of funds from the parent
drug company.

References.

1. Halliwell B, Cross C Reactive Oxygen Species, Antioxidants, and Acquired 
Immunodeficiency Syndrome,Arch Intern Med. Vol 151, Jan 1991 pp. 29-31.

2. Halliwell B, Free radicals, reactive oxygen species and human disease: a 
critical evaluation with special reference to artherosclerosis. Br J ExpPathol. 
1989;70:737-757.

3. Diplock A, Antioxidant nutrients and disease prevention: an overview, Am J 
Clin Nutr 1991;53:189S-93S.

4. Staal FJT, Roederer M, Herzenberg LA, Herzenberg LA, Intracellular thiols 
regulate activation of nuclear factor kB and transcription of human 
immunodeficiency virus. Proc Natl Acad Sci USA 1990;87:9943-47.

5. Kalebic T, Kinter A, Poli G, Anderson ME, Meister A, Fauci AS, 
Suppression of HIV expression in chronically infected monocytic cells by 
glutathione, glutathione ester, and N-acetylcysteine. Proc Natl Acad Sci USA 
1991;88:986-90.

6. Mihm S, Ennen J, Pessara U, Kurth R, Droge W, Inhibition of HIV-1 
replication and NF-kB activity by cysteine and cysteine derivatives. AIDS 
1991,5:497-503.

7. Staal FJ, Ela SW, Roederer M, Anderson MT, Herzenberg LA, Herzenberg 
LA. Glutathione deficiency and human immunodeficiency virus infection. 
Lancet,1992;339(8798):909-912.

8. Buhl R, Jaffe HA, Holroyd KJ, Wells FB, Mastrangeli A, Saltini C,
Cantin AM, Crystal RG. Systemic Glutathione Deficiency in
Symptom-Free HIV-Seropositive Individuals. Lancet 1989;ii:1294-98.

9. Eck H-P,Gmunder H, Hartmann M, Petzoldt D,Daniel V, Droge W, Low 
concentrations of acid-soluble thiol (cysteine) in the blood plasma of HIV-1 
infected patients. Biol Chem Hoppe Seyler 1989;370:101-08.

10. Roederer M, Staal FJT, Osada H, Herzenberg LA, Herzenberg LA. CD4 
and CD8 T cells with high intracellular glutathione levels are selectively lost as 
the HIV infection progresses. Int Immunol 1991;3:933-37.

11. Droge W. Pharmacology, 1993;46(2):61-5

12. Roederer M, Staal FJT, Raju PA, Ela SW, Herzenberg LA, Herzenberg LA. 
Cytokine stimulated HIV replication is inhibited by N-acetylcysteine. Proc Natl 
Acad Sci USA 1990;87:4884-88.

13. Roederer M, Raju PA, Staal FJT, Herzemberg LA, Herzenberg LA.
N-acetylcysteine inhibits latent HIV expression in chronically
infected cells. AIDS Res Hum Retroviruses 1991;7:563-67.

14. Levy EM et al Cell Immunol, 1992;140(2):370-80.

15. Harakeh S, Jariwalla RJ. Comparative study of the anti-HIV activities of 
ascorbate and thiol-containing educing agents in chronically HIV-infected 
cells. Am J Clin Nutr 1991;54:1231S-5S.

16. []ioy J et al J Clin Inv, 1993;91(2):495-8.

17. Lederman M et al L-2 oxothiazolidine-4-carboxylate (Procysteine) inhibits 
HIV-1 expression but not interleukin-2 secretion. Abstract PO-A28-0681, IX Intl 
Conf, Berlin, 1993.

18. Williamson JM et al Intracellular cysteine delivery system that protects 
against toxicity by promoting glutathione synthesis PNAS 79:6245-9, 1982.

19. Fidelus RK et al Enhancement of intracellular glutathione promotes 
lymphocyte activation by mitogen, Cellular Immunol 97:155-63, 1986.

20. de Quay B, Malinverni R, Lauterburg B. Glutathione depletion in 
HIV-infected patients: role of cysteine deficiency and effect of oral
N-acetylcysteine, AIDS 1992;6(8):815-819.

21. James J (ed) AIDS Treatment News, Oct.1993 #184.

22. Skowron G et al A phase I trial of oral Procysteine
(L-2-oxothiazolidine-4- carboxylate) in early HIV infection. Abstract
PO-B-29-2177, IX Intl Conf AIDS, Berlin, 1993.


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Evaluating New or "Alternative" Treatments
 by Kevin Armington

Do not rely on only one source to make your decision. 

Discuss potential treatment options with your health care providers
and friends. If your doctor will not engage in a dialogue about
alternative therapies, you may want to consider changing doctors or
consulting with another physician. 

Getting a new doctor may not be so easy for people with limited or no
insurance. Call some reliable hotlines and explore your options (GMHC:
212/807-6655; Project Inform. 415/558-9051 in California, 800/822-7422
outside of CA). Some hotlines keep doctor referral lists and others
dispense information about treatments. Most importantly, do not make
your decision in a vacuum.

Beware of claims that a treatment is a "cure" or will have miraculous
effects. We all want to be optimistic, but there is nothing crueler
than overblown reports about new treatments. Individuals or
publications that make uninformed promises about a treatment before
it has been adequately researched increase confusion and can
ultimately hurt people. Claims must be substantiated by 
understandable information about safety in people with HIV infection
and proof that the treatment has, or could have some beneficial
effect.

Prohibitively high prices for experimental treatments can be the
tip-off to potential fraud. The costs of alternative treatments are
absorbed by the individual, since it is extremely rare for insurance
companies or Medicaid to reimburse for treatments that are not drugs
licensed by the FDA. Unfortunately, there is no shortage of
charlatans willing to take huge sums of money for unproven and
sometimes even harmful "treatments."

Try to investigate any clinic you may visit; have a friend look into
it if you cannot do so yourself. There are several examples of
clinics in the U.S. and abroad that offer expensive treatment
packages. Usually, treatment requires in- patient stays for several
weeks. Some of these ventures require strenuous travel to remote
parts of the world. Besides financial considerations, risks may 
include substandard medical care and exposure to unfamiliar
disease-causing microorganisms, which can strain the immune system.
If no independent information is available about the clinic, it may
be a negative sign. No clinic has come forth with any magic answers
yet. Some, after having charged a fortune, send people home sicker
than when they arrived.

Interview the treatment promoter. If you are considering trying an
unproven treatment, be a smart consumer and interview the person
promoting it. How much do they know about AIDS and HIV? If they
reject commonly accepted theories about AIDS, are they at least
familiar with these theories? What is their training? Are they
interested in specific information about your medical condition, or
are you treated as a faceless customer? Do they answer your questions
patiently in language you understand or do they "talk down" to you? 
Are their explanations about the treatment overly simplistic or overly
complex? Do they seem eager to foster a sense of distrust between you
and your current health care providers? Is there an attempt to
separate you from your current network of support? How has their
treatment been evaluated so far? And what is the justification for
using their treatment for AIDS?

If the treatment has not been objectively evaluated (published in a 
peer-reviewed medical journal or presented at a significant AIDS
medical conference) proceed with caution. Consult with your current
health care providers and friends who are familiar with AIDS. Trust
your vibes. If you have a funny feeling about someone pitching a
treatment, listen to your instincts and try not to act spontaneously.
You deserve honest, direct answers to any questions you may have.

Beware of Media Distortion. There is a familiar scenario that
characterizes public awareness of new potential treatments for HIV
disease. It goes something like this: an item on television or in the
newspaper reports a claim that a "cure" for AIDS has been discovered;
many people with AIDS begin a furious quest to obtain the treatment;
the initial positive results are not reproduced in further studies;
scrutiny reveals that the groundbreaking reports were blown out of
proportion; a sense of hopelessness sets in. This cycle has been
dubbed the "drug-of-the-month" phenomenon. With a few notable 
examples, the lay media has done an inaccurate job reporting on AIDS 
treatments. News reports and articles on AIDS treatments tend to focus
on the most sensational aspect of the story. Often the facts are
either absent or utterly distorted. Inaccurate reports can create
very damaging impressions in the community. In general, the lay media
probably reports information too early. Splashy accounts of drugs
that have great antiviral effect in the test tube make good copy, but
have limited value to most people. Only a small fraction of drugs
make it from the laboratory to the pharmacy.

Seek out a variety of opinions to reduce possible bias. Even community
publications can have a very predictable editorial slant, calling
their objectivity into question. Some receive funds from
pharmaceutical companies that manufacture AIDS therapies. While there
may be nothing wrong with this, particularly given the low level of
funding of not for profit AIDS organizations, such financial support
should be clearly identified. In general, it is not a good idea to
rely on one source for your treatment information. There are certainly
plenty of treatment publications available free or at low cost. (See
"AIDS Treatment Resources" Treatment Issues, October 1993, for a
partial list).

Let your health care provider know exactly what treatments you are
taking. Whatever treatments you decide to use, make sure you inform
your healthcare provider. Some therapies can have unique side effects
which may be misdiagnosed if your health care provider does not about
them. Additionally, some therapies may have harmful interactions with
existing medications.


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The Dietary Supplement Health and Education Act of 1993 (S.784/H.R.1709)
 by Derek Hodel

 One pill makes you larger
 And one pill makes you small,
 And the ones that mother gives you
 Don't do anything at all...
 - Jefferson Airplane "White Rabbit" (1967)[1]

A bill now before Congress, the Dietary Supplement Health and
Education Act of 1993, has attracted considerable attention within
the AIDS community and elsewhere. The Act was written in response to
FDA rulemaking, and would significantly change the authority of FDA
to regulate the dietary supplements marketplace. Sales of such
supplements, to an estimated 60 million consumers, exceed $3 billion
annually.[2] 

The bill was introduced by Senator Orrin Hatch [R/UT] in the Senate
and by Representative Bill Richardson [D/NM] in the House of
Representatives, and has accumulated an impressive, bipartisan array
of sponsors.[3] In the Senate, the bill is currently in committee,
where significantly, Senator Edward Kennedy [D/MA], Chairman of the
Labor and Human Resources Committee of the Senate, has expressed
strong reservations. In the House, Representative Henry Waxman
[D/CA], Chairman of the Health and Environment Subcommittee of the
Committee on Energy and Commerce, has also voiced strong objections 
to the bill. 

At balance are FDA's mandate to protect consumers from dangerous
products and fraudulent health claims versus the consumer's "right to
know" and freedom to choose.[4] The current debate represents only
the most recent installment in a long-standing dispute between the
industry and the agency[5], and was spurred by the Nutrition Labeling
and Education Act of 1990 (NLEA).  In the NLEA, Congress directed FDA
to develop regulations governing health claims for foods, requiring
that such claims be supported by "significant scientific agreement."
The act resulted in substantial changes in labeling on grocery
shelves, and reduced significantly the health claims that had become 
commonplace on everything from oat bran muffins to orange juice. The
NLEA also required FDA for the first time to promulgate rules
governing health claims for dietary supplements[6] - and here is
where the trouble began.

Because the statute did not specify a scientific standard for health
claims for dietary supplements, as it had for traditional foods, the
matter was left to FDA discretion. The agency, arguing that to set a
standard different for supplements than for foods would be illogical
and would provide consumers with contradictory and confusing
information, proposed rules that set the same, "significant
scientific agreement" standard. 

The supplements industry, faced with significant restrictions on what
had become commonplace labeling claims[7], lobbied hard for
Congressional relief. In response, the Dietary Supplement Act was
appended to FDA user-fee legislation during the final sessions of the
102nd Congress. The Act, required FDA to propose rules governing
health claims by June 15, 1993 and to finalize such rules by December
15, 1993. 

In the intervening year, FDA released the final report of the Dietary
Supplements Task Force, an internal agency task force that
Commissioner David Kessler had charged with examining the regulatory
issues surrounding dietary supplements, for public comment.[8]
Previously, the agency had also commissioned the Federation of
American Societies for Experimental Biology (FASEB) to review the
scientific literature concerning the safety of amino acids - this
report was released for public comment, as well.[9] Lastly, FDA did 
issue a final rule using the "significant scientific agreement"
standard, already in force in the foods industry, as a means of
regulating dietary supplements.

The Dietary Supplement Health and Education Act of 1993 anticipates
the FDA rulemaking now under way, and carves out a separate
regulatory class for dietary supplements that is more lenient than
for traditional foods. In essence, the Act prohibits FDA from
regulating dietary supplements under either the "drug" or "food
additive" provisions of the Food, Drug and Cosmetic Act. Most 
notably, it also shifts the burden of proof of safety from the
manufacturer to the FDA. In other words, it would be up to the agency
to prove in court action that a particular supplement or ingredient
was not safe, prior to enforcement action, rather than a
manufacturer's obligation to prove that it was. 

Strikingly, health claims would also be permitted, as long as they
"accurately represent the current state of scientific evidence
concerning the relationship between the supplement or dietary
ingredient of the supplement and a disease or other health-related
condition," a determination that would be left to the manufacturer
(rather than to FDA) to make, a sharp curtailment of, and 
philosophical departure from, the "significant scientific agreement"
standard. In effect, health claims that are currently not permitted
on a carton of orange juice, could be permitted on bottles of Vitamin
C. 

The supplements industry, represented by the National Nutritional
Foods Association (NNFA) and others, is waging an aggressive lobbying
campaign in favor of the Hatch/Richardson Act and against the FDA
rules. One very slick television spot features Mel Gibson, attired in
bathrobe and holding a bottle of Vitamin C, being accosted in his
home by an FDA "SWAT team." 

Congressional aides have reported receiving "thousands" of letters
from consumers, who are fearful that products on which they have come
to depend may be removed from the marketplace. Much reporting on the
issue, particularly in the lay AIDS press, has been vastly
overwrought, with some reporters suggesting that FDA proposals would
mandate that all such supplements would require a prescription from a
doctor, or that herbs would simply be removed wholesale from the
market, or that FDA is intent on shutting down the health foods
industry. 

For the AIDS community, the issue poses a particularly acute dilemma.
Many people with HIV view supplements as an effective component of
their treatment regimen. In testimony before Waxman's committee, Fred
Bingham, Executive Director of DAAIR (Direct AIDS Alternative
Information Resources) claimed that his T-cell count increased from
30 to over 900 and stabilized for two years "by using a combination
of anti-oxidants, amino acids, and herbs, including an IV 
pharmaceutical preparation of licorice, called glycyrrhizin..."[10]
Although Bingham spoke in favor of "full disclosure labels" and
"non-misleading claims," the nexus of his testimony rested on alleged
FDA institutional bias. Bingham claimed that FDA's concerns about the
safety of amino acids, for example, was "pure politically motivated
bias." In a credo typical of the tone of debate, Bingham said, "As a
person living with AIDS, my very life depends on continued access to
the supplements that the FDA apparently considers to be a threat to
drug development."

The emotional tenor of the debate, combined with the usual cloud of
smoke generated by Washington lobbyists, will make the issue a
difficult one for the AIDS community to resolve. It is fair to say
that there is a significant problem with fraudulent health claims,
particularly in the dietary supplement marketplace, and that many of
those claims are aimed directly at people with AIDS. Conversely,
people living with HIV disease, faced with narrow enough (and mostly
inadequate) treatment options from so-called mainstream providers, 
are understandably concerned with the prospect that their options
might be further diminished. 

Although the trajectory of the Dietary Supplement Health and Education
Act of 1993 is uncertain, given the level of public interest and
Congressional lobbying, it seems likely that it will assume a
prominent position in the agenda of the AIDS community for some time.

1. As quoted in Frank, Richard L. and O'Flaherty, Michael J., "The
Battle Gets Curiouser and Curiouser." Legal Times (September 20,
1993): 29-30.

2. Over 80% of "dietary supplements" are vitamins and minerals, which
according to FDA, can fairly be called "nutritional supplements,"
since they are known to play a well understood role in human
nutrition. Further, the agency says that such vitamins and minerals
present no particular regulatory concern, when manufactured safely
and when sold without unsupported health claims and in reasonable
potencies. In terms of the current debate, "dietary supplement" is
also being used to describe a variety of herbs, high-potency amino
acids (such as those marketed to body-builders), and other products.

3. As of 18 October 1993, Senator Hatch reports 59 Senate cosponsors, 
enough to pass the bill. In the House, Richardson has accumulated 158 
cosponsors, which include such odd ideological bedfellows as Reps. Pelosi, 
Holmes-Norton, Hall and Tauzin.

4. FDA's authority to regulate foods (which generally require no
pre-marketing approval) and drugs (which do) is vested in the Food,
Drug and Cosmetic Act of 1938. In 1958, Congress passed the Food
Additive Amendments, which authorize FDA to require premarketing
approval of additives not generally recognized as safe. After FDA
proposed rules in the 1970's to regulate dietary supplements by
specifying composition and potency, Congress passed the Proxmire
Amendments, which prohibit FDA from limiting the maximum potency of
vitamin and mineral supplements, except where the agency can
demonstrate safety problems. 

5. FDA reports directing only 1% of its enforcement resources toward
dietary supplements. In the last three years, this amounted to 40
legal actions.

6. Traditionally, FDA had initiated enforcement actions against
dietary supplements, either for misleading health claims or safety
concerns, under the food additive or drug provisions of the Food,
Drug and Cosmetic Act. Two recent court cases determined that FDA
could not apply the food additive provisions of the Food, Drug and
Cosmetic Act to a single nutrient. Since these provisions provide the
basis for most enforcement actions in this arena, if these court
cases stand, FDA jurisdiction in this arena would be sharply
curtailed.

7. FDA published a report, Unsubstantiated Claims and Documented
Health Hazards in the Dietary Supplement Marketplace, illustrating a
vast, and troubling, array of clearly fraudulent health claims.
(Hundreds of examples are included. For instance, the House of
Hezekiah produces "Suma," which it claims "strengthens the immune
system; reduces tumors and cancers;" a multitude of companies produce
products claimed to be effective against AIDS, including Crystal Star
Herbal Nutrition's "Biotec Extra Energy Enzymes.")

8. Dietary Supplements Task Force: Final Report. Washington, DC:
Department of Health and Human Service, Public Health Service, Food
and Drug Administration, May, 1992. The report, which does not
represent current agency policy, recommends that FDA: 1) determine
maximum safe intake levels for vitamins and minerals; 2) initiate
rulemaking to categorize many amino acid products as drugs; 3)
continue to apply the "food additive" standard to most dietary
supplement products, unless drug claims are made; and 4) implement
good manufacturing practice standards.

9. FASEB advised that there was insufficient data to determine safe
levels of intake for amino acids, and recommended that the young, the
elderly, women of childbearing age, smokers, and other potentially
vulnerable subgroups use these products only under medical
supervision. Concern surrounding amino acid toxicity had been
generated by the voluntary recall of L-tryptophan, the ingestion of
which published reports had associated with an epidemic of 
eosinophilia myalgia syndrome (EMS), a connective tissue disease which
claimed 38 lives and injured 1500. After extensive investigations, FDA
remains unable to conclusively determine the role of L-tryptophan in
associated outbreaks of EMS. Although some studies suggest that
contamination may have played a role, other studies demonstrate an
association between the disease and L-tryptophan with no known
contamination. The episode is instructive, in that current law
permitted FDA to act swiftly - presumably, under S.784/H.R.1709, the
burden of proving safety would be shifted to FDA, prior to 
enforcement action.

10. Bingham, Fred. Testimony before the House Subcommittee on Health
and the Environment, Committee on Energy and Commerce. July 29, 1993.