Clinical Trials with Glutathione, Whey
Protein
Clinical Trials in
HIV-AIDS
Whey
proteins as a food supplement in HIV-seropositive
individuals. Bounous G, Baruchel S, Falutz J, Gold P. Department of
Surgery, Montreal General Hospital, Quebec. [Clin Invest Med 1993
Jun;16(3):204-9] On the basis of numerous animal experiments, a pilot
study was undertaken to evaluate the effect of undenatured, biologically
active, dietary whey protein in 3 HIV-seropositive individuals over a
period of 3 months. Whey protein concentrate was prepared so that
the most thermosensitive proteins, such as serum albumin which contains
6 glutamylcysteine groups, would be in undenatured form. Whey protein
powder dissolved in a drink of the patient's choice was drunk cold in
quantities that were increased progressively from 8.4 to 39.2 g per day.
Patients took whey proteins without adverse side effects. In the 3
patients whose body weight had been stable in the preceding 2 months,
weight gain increased progressively between 2 and 7 kg, with 2 of the
patients reaching ideal body weight. Serum proteins, including
albumin, remained unchanged and within normal range, indicating that
protein replenishment per se was not likely the cause of increased body
weight. The glutathione content of the blood mononuclear cells was, as
expected, below normal values in all patients at the beginning of the
study. Over the 3-month period, glutathione levels increased in all 3
cases. In conclusion, these preliminary data indicate that, in
patients who maintain an adequate total caloric intake, the addition
of "bioactive" whey protein concentrate as a significant portion of
total protein intake increases body weight and shows elevation of
glutathione (GSH) content of mononuclear cells toward normal levels.
This pilot study will serve as a basis for a much larger clinical trial.
Publication Types: Clinical Trial
Join a clinical study: (Canadian HIV Trials Network) CTN79:
Multicentre, Double-blind, randomized control study of whey protein
concentrate (this product) vs. Casein in
patients with AIDS and wasting syndrome One study of
this all-natural product concluded that this "whey protein concentrate"
a derivative of cows milk, is completely safe for people who have been
diagnosed as lactose-intolerant. This analysis has lead to the funding
of phase 3, clinical trial on adult AIDS patients with wasting
syndrome. About the
study: Treating AIDS-related wasting syndrome with a whey protein
concentrate (WPC) may combat the negative effect of oxidative
stress, improve T-cell function and T-cell
survival, as well as aid in the control of HIV replication. The
study's primary objectives are to determine the effect of WPC on
nutrition in patients with AIDS-related wasting syndrome, and to
determine the glutathione-changing activity of WPC in people with
AIDS-related wasting syndrome. After a one-month screening period,
each volunteer will be randomized to Diet Regimen A (WPC) or Diet
Regimen B (casein - another milk product used as a control). Treatment
will continue for six months. Researchers will monitor weight gain to
judge the efficacy of the treatment.
CTN
(Canadian HIV Trials Network) Trial Results - Whey protein supplementation
CTN043: Whey Protein
Supplementation in HIV-Infected Children: A Pilot Study
Objective:
This study assessed the value of whey protein, a milk supplement, to
prevent severe weight loss in children with AIDS. Study Design: This
was an open label, pilot study (both investigators and volunteers knew
which treatment was being given), with only one study group.
Participants received daily oral supplementation of whey protein, given
as a powder at a starting dose based on 20% of the total daily protein
requirement, and increased by increments of five percent every month
during four months to reach 35% of the total protein intake at the end
of the six-month study. Study Population: Fourteen children were
enrolled in four centres. Essential requirements for study entry
included wasting syndrome (severe weight loss) within the six
months preceding entry into the study. Of 14 participants enrolled, 11
were evaluated. The age of the participants ranged from eight months to
15 years. Results: None of the children experienced any toxicity
(side effects) such as diarrhea, vomiting or milk intolerance.
All of them gained weight, between 3.2% and 18% from their
starting weight. Eight demonstrated improvements in growth parameters,
such as in tricep skinfolds, with mid-arm muscle circumference
increasing from +1.2% to +25% independently of energy intake. No changes
were found in CD4 cell count, but two children experienced a
significant increase in CD8 cell count. Conclusions: Whey protein
is very well-tolerated in children with AIDS, and it was shown to
improve nutrition and growth in a subgroup of patients.
Glutathione
deficiency is associated with impaired survival in HIV disease.
Herzenberg LA, De Rosa SC, Dubs JG, Roederer M, Anderson MT, Ela SW,
Deresinski SC, Herzenberg LA. Department of Genetics, Stanford
University Medical School, CA 94305-5125, USA. Glutathione (GSH), a
cysteine-containing tripeptide, is essential for the viability and
function of virtually all cells. In vitro studies showing that low GSH
levels both promote HIV expression and impair T cell function suggested
a link between GSH depletion and HIV disease progression. Clinical
studies presented here directly demonstrate that low GSH levels predict
poor survival in otherwise indistinguishable HIV-infected subjects.
Specifically, we show that GSH deficiency in CD4 T cells from such
subjects is associated with markedly decreased survival 2-3 years
after baseline data collection. This finding, supported by evidence
demonstrating that oral administration of the GSH prodrug
N-acetylcysteine replenishes GSH in these subjects and suggesting that
N-acetylcysteine administration can improve their survival,
establishes GSH deficiency as a key determinant of survival in HIV
disease. Further, it argues strongly that the unnecessary or
excessive use of acetaminophen, alcohol, or other drugs known to deplete
GSH should be avoided by HIV-infected individuals.
Publication
Types: Clinical Trial
Randomized Controlled Trial
Stanford NAC Study:
Glutathione Level Predicts Survival Author: John S. James
[AIDS Treatment News; Issue: 266 03/07/97] A small randomized
controlled trial of oral N-acetylcysteine(NAC) was run in San Francisco
in 1993 and 1994. A report from this study was published in the PROCEEDINGS
OF THE NATIONAL ACADEMY OF SCIENCES, USA (1); it was also presented
at a major immunology conference in San Francisco on February 22,
receiving television and newspaper coverage. The basic findings were:
(1) For persons with a CD4 count under 200, an abnormally low level
of glutathione -- inside CD4 T-cells in the blood --was remarkably
predictive of poor survival. (Glutathione is the major defense of
those cells against oxidative stress.) Persons with a CD4 count under
200, who also had very low glutathione levels, had an estimated
three-year survival a slow as 20 percent -- compared to 60 to 80 percent
survival for those with CD4 below 200 but with adequate glutathione
levels. (Survival results were presented for those with CD4 counts
under 200, since in the three years after the blood measurement, there
were not enough deaths to analyze in those with counts above 200.
However, the survival difference was also statistically significant when
everyone was included regardless of CD4 count.) (2) Oral NAC helped
to replenish low glutathione in blood cells. These findings alone do
not prove that NAC is beneficial. However, followup studies two to
three years later showed that persons who were given or chose to take
NAC during the trial had considerably better survival than similar
subjects who did not take NAC. But since the trial was not set up to
make this comparison, the researchers emphasize that a larger controlled
trial will be needed to determine for sure whether NAC has
benefit.
N- acetylcysteine replenishes glutathione in HIV
infection. De Rosa SC, Zaretsky MD, Dubs JG, and others. [Eur J Clin
Invest 2000 Oct;30(10):915-29.] Comment
in: Eur J Clin Invest. 2000 Oct;30(10):841-2. Glutathione (GSH)
deficiency is common in HIV-infected individuals and is associated with
impaired T cell function and impaired survival. N-acetylcysteine
(NAC) is used to replenish GSH that has been depleted by acetaminophen
overdose. Studies here test oral administration of NAC for safe and
effective GSH replenishment in HIV infection. Whole blood GSH levels
in NAC arm subjects significantly increased, bringing GSH levels in
NAC-treated subjects to 89% of uninfected controls. Baseline GSH levels
in the placebo group remained essentially the same during the 8 week
placebo-controlled trial. T cell GSH, adjusted for CD4 T cell
count and beta2-microglobulin levels, also increased in the NAC-treated
subjects. Adverse effects were minimal and not significantly
associated with NAC ingestion. NAC treatment for 8 weeks safely
replenishes whole blood GSH and T cell GSH in HIV-infected individuals.
Thus, NAC offers useful adjunct therapy to increase protection
against oxidative stress, improve immune system function and increase
detoxification of acetaminophen and other drugs. These findings suggest
that NAC therapy could be valuable in other clinical situations in
which GSH deficiency or oxidative stress plays a role in disease
pathology.
Publication Types: Clinical Trial
Randomized
Controlled Trial
Currently there are clinical trials being conducted
at the Center for Disease Control in Atlanta Ga. which has
favorably reported on the use of this product for extending life to AIDS
patients.
Ongoing studies at McGill University in Quebec
Canada, with amazing results in the treatment & remission of
various cancers such as prostrate, breast & extended life to AIDS
patients.
Phase III clinical trial
(Canada HIV Network) studies, Montreal General Hospital.
Clinical Trials in
Cancer
The
use of a whey protein concentrate in the treatment of patients with
metastatic carcinoma: a phase I-II clinical study. Kennedy
RS, Konok GP, Bounous G, Baruchel S, Lee TD. [Anticancer Res. 1995
Nov-Dec;15(6B):2643-9.] Glutathione (GSH) concentration is high in most
tumour cells and this may be an important factor in resistance to
chemotherapy.........experiments have shown a differential response of
tumour versus normal cells to various cysteine delivery
systems.........at concentrations that induce GSH synthesis in normal
human cells, a specially prepared whey protein concentrate, this product,
caused GSH depletion and inhibition of proliferation in human breast
cancer cells. On the basis of this information five patients with
metastatic carcinoma of the breast, one of the pancreas and one of the
liver were fed 30 grams of this whey protein concentrate daily for six
months.......The results indicate that whey protein concentrate might
deplete tumour cells of GSH and render them more vulnerable to
chemotherapy.
Glutathione
reduces the toxicity and improves quality of life of women diagnosed
with ovarian cancer treated with cisplatin: results of a double-blind,
randomised trial. Smyth JF, Bowman A, Perren T, Wilkinson P,
Prescott RJ, Quinn KJ, Tedeschi M. ICRF Medical Oncology Unit,
Western General Hospital, Edinburgh, UK. [Ann Oncol 1997
Jun;8(6):569-73] BACKGROUND: Early clinical trials have suggested
that glutathione (GSH) offers protection from the toxic effects of
cisplatin. Quality of life scores demonstrated that for patients
receiving GSH there was a statistically significant improvement in
depression, emesis, peripheral neurotoxicity, hair loss, shortness of
breath and difficulty concentrating. As an indication of overall
activity, these patients were statistically significantly more able to
undertake housekeeping and shopping. Clinically assessed response to
treatment demonstrated a trend towards a better outcome in the GSH
group (73% versus 62%) but this was not statistically significant (P
= 0.25). CONCLUSIONS: The results demonstrate that adding GSH to CDDP
allows more cycles of CDDP treatment to be administered because less
toxicity is observed and the patient's quality of life is improved.
Publication Types: Clinical Trial
Randomized Controlled
Trial
German
study finds whey protein supplement boosts antioxidants.
[Treatmentupdate 2001 May;13(1):2]
Publication Types: Clinical Trial
Newspaper Article
The Nova Scotia Cancer Research Center has
undertaken a phase 2 trial on breast cancer patients based on a
study from Department of Surgery at Dalhousie University, Halifax, Nova
Scotia Canada.
The University of Munich, Germany are conducting
tests on patients following major surgery & multiple trauma.
Plus, a trial is underway at the King Khalid Hospital, Jeddah, Saudi
Arabia involving children during the course of chemotherapy for the
treatment of Leukemia.
Ongoing studies at McGill University in Quebec
Canada, with amazing results in the treatment & remission of
various cancers such as prostrate, breast & extended life to AIDS
patients.
World-wide clinical studies on cancer
include:
- Phase II trial on breast cancer,
Halifax, Canada.
- Phase II trial on breast cancer, Nova
Scotia Cancer Center.
- A 1995
Phase I-II clinical trial in the treatment of patients with
metastatic carcinoma (Department of Surgery, Dalhousie
University, Halifax, Nova Scotia, Canada)
- Trial in prostatic cancer, Royal
Victoria Hospital.
- Current in vitro study on renal, prostatic,
and bladder cancer cell lines at a major Boston university.
Nutritional therapy of chronic hepatitis by whey protein
(non-heated). Watanabe A, Okada K, Shimizu Y, Wakabayashi H, Higuchi K,
Niiya K, Kuwabara Y, Yasuyama T, Ito H, Tsukishiro T, Kondoh Y, Emi N,
Kohri H. [J Med 2000;31(5-6):283-302] In an open study the
clinical efficacy of milk serum (whey) protein (this product; cysteine
content: 7.6-fold higher than that of casein) isolated from fresh milk
and purified without heating was evaluated in 25 patients with chronic
hepatitis B or C. this product (12 g as protein) food (mousse) was
given twice a day, in the morning and evening, for 12 weeks (test
period). Casein (12 g as protein) food (mousse) was similarly given for
two weeks prior to the start of the supplement with this product food
(induction period) and for four weeks after the end of the supplement
with this product food (follow-up period). Serum alanine aminotransferase
(ALT) activity was reduced, and plasma glutathione (GSH) levels
increased in six and five of eight patients with chronic hepatitis
B, respectively, 12 weeks after the start of the supplement with
this product food. Serum lipid peroxide levels significantly decreased, and
interleukin (IL)-2 levels and natural killer (NK) activity significantly
increased. However, there were no significant this product-related changes
in 17 patients with chronic hepatitis C. These findings suggest that
the long-term supplement with this product alone may be effective for
improving liver dysfunctions in patients with chronic hepatitis B.
Publication Types: Clinical Trial
Other World-wide clinical studies
include:
- Lyme disease study, Springfield,
Illinois.
- Major surgery and multiple trauma
study, University of Munich, Germany.
- Phase III clinical trial (Canada HIV
Network) studies, Montreal General Hospital.
- Trial in Cystic fibrosis, Montreal
Children's Hospital.
- 30-week, Multi-center, single-blind,
placebo-controlled this product
Chronic Fatigue and Immune Dysfunction Syndrome (CFIDS) trial
is currently underway (6/2000) among 75 CFIDS patients in
Canada, the United States, and the United Kingdom.
