1- COMPETITION
FOR GLUTATHIONE PRECURSORS BETWEEN THE IMMUNE SYSTEM AND THE SKELETAL MUSCLE: PATHOGENESIS OF CHRONIC FATIGUE SYNDROME.
G.
Bounous1, J Molson2
1 Former Professor, Department of Surgery,
McGill University, and career Investigation of the Medical Research Council of
Canada
2 1994
Quebec Cycling Champion. Road and Time Trial
SUMMARY - The chronic fatigue syndrome (CFS) is
typically associated or follows a recognized or presumed infection.
Abnormalities of both humoral and cellular immunity have been demonstrated in a
substantial proportion of patients with CFS. The most consistent findings are
of impaired lymphocyte responses to mitogen. As an antioxidant, glutathione
(GSH) is essential for allowing the lymphocyte to express its full potential
without being hampered by oxiradical accumulation. Hence, protracted challenge
of the immunocytes may lead to cellular GSH depletion.
Because GSH is also essential to
aerobic muscular contraction, an undesirable competition for GSH precursors
between the immune and muscular systems may develop. It is conceivable that the
priority of the immune system for the survival of the host has drawn to this
vital area the ever-diminishing GSH precursors, thus depriving the skeletal
muscle of adequate GSH precursors to sustain a normal aerobic metabolism
resulting in fatigue and eventually myalgia. © 1999 Harcourt Publishers Ltd.
Anticancer RESEARCH 15:
2643-2650, 1995
2-
THE USE OF A WHEY PROTEIN CONCENTRATE IN THE TREATMENT OF
PATIENTS
WITH METASTATIC CARCINOMA: A PHASE I-II CLINICAL STUDY
RENEE
S. KENNEDY1, GEORGE P. KONOK1, GUSTAVO BOUNOUS2,
SYLVAIN BARUCHEL3
and
TIMOTHY D.G. LEE4
1Department
of Surgery, Dalhousie University, Halifax, Nova Scotia:
2Department
of Surgery, McGill University, Montreal Quebec
3Department of Pediatrics and Oncology,
McGill University, Montreal, Quebec: 4Department of Immunology and
Microbiology, Dalhousie University, Halifax, Nova Scotia, Canada
ABSTRACT. Glutathione (GSH)
concentration is high in most tumor cells and this may be an important factor
in resistance to chemotherapy. Previous in-vitro and animal experiments have
shown a differential response of tumor versus normal cells to various cysteine
delivery systems. More specifically, an in-vitro assay showed that at
concentrations that induce GSH synthesis in normal human cells, a specially
prepared whey protein concentrate, Immunocal™, 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. In six patients the blood lymphocyte GSH
levels were substantially above normal at the outset, reflecting high tumor GSH
levels. Two patients (#1, #3) exhibited signs of tumor regression,
normalization of haemoglobin and peripheral lymphocyte counts and a sustained
drop of lymphocyte GSH levels towards normal. Two patients (#2, #7) showed
stabilization of the tumor, increased haemoglobin levels. In three patients
(#4, #5, #6) the disease progressed with a trend toward higher lymphocyte GSH
levels. These results indicate that whey protein concentrate might deplete
tumor cells of GSH and render than more vulnerable to chemotherapy.
3-
WHEY PROTEINS AS A FOOD SUPPLEMENT IN HIV-SEROPOSITIVE
INDIVIDUALS
G.
Bounous, S. Baruchel, J. Falutz, P. Gold
Departments
of Surgery and Medicine, The Montreal General Hospital and McGill University,
Montreal, Quebec
ABSTRACT – 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, GSH levels increased and in one case rose by 70% to
reach normal value. The increase in body weight observed in these patients did
not correlate with increase in energy or protein intake.
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.
CLIN INVEST MED, 14: 296-309, 1991
ROLE
OF GLUTATHIONE.
G.
Bounous, P. Gold
Department
of Surgery, Montreal General Hospital, Research Institute, Quebec
ABSTRACT – This study compared the
effects of different sources of whey protein concentrate (20 g/100 g diet) and
of casein on the spleen, liver, and heart glutathione content of C3H/HeJ mice,
and on the immune response of their spleen cells to sheep red blood cells. Body
weight curves were similar in all dietary groups. Our data indicate that the
humoral immune response is highest in mice fed a dietary whey protein
concentrate exhibiting the highest solubility (undenatured conformation) and a greater
relative concentration of the thermolabile cystine rich proteins. In addition,
the mice fed this type of whey protein concentrate exhibit higher levels of
tissue glutathione. The presence in the serum albumin fraction of
glutamylcysteine groups (rare in food protein) and the specific intramolecular
bond as related to the undenatured conformation of the molecule are considered
to be key factors in the glutathione-promoting activity of the protein mixture.
CANCER LETTERS, 57: 91-94, 1991
5- WHEY PROTEINS IN CANCER PREVENTION.
ABSTRACT – Epidemiological and
experimental studies suggest that dietary milk products may exert an inhibitory
effect on the development of several types of tumors. Some recent experiments
in rodents indicate that the antitumor activity of the dairy products is in the
protein fraction and more specifically in the whey protein component of milk.
We and others have demonstrated that whey protein diets result in increased
glutathione (GSH) concentration in a number of tissues, and that some of the
beneficial effects of whey protein intake are abrogated by inhibition of GSH
synthesis. Whey protein is particularly rich in substrates for GSH synthesis.
We suggest that whey protein may be exerting its effect on carcinogenesis by
enhancing GSH concentration.
TUMOR BIOL 11: 129-136, 1990
6-
DIETARY MILK PROTEINS INHIBIT THE DEVELOPMENT OF
DIMETHYLHYDRAZINE-INDUCED
MALIGNANCY
R.
Papenburga, G. Bounousa, D. Fleiszera, P. Goldb
Departments
of aSurgery and bMedicine, The Montreal General Hospital
and McGill University,
Montreal,
Quebec, Canada
ABSTRACT – This study investigated the
influence of two formula diets containing 20 g/100 g diet of either whey
protein concentrate or casein, or Purina mouse chow on 1,2dimethylhydrazine
(DMH)-induced colon carcinoma in A/J mice. Four weeks after the 24th
DMH treatment the incidence of tumour and tumour area in the whey protein-fed
mice was substantially less in comparison to either the casein or Purina
groups. The Purina group exhibited the greatest tumour burden. At the end of
the experiment all animals continuously fed the whey protein diet were found to
be alive, whereas 33% of those on the casein or Purina diet had died. Animals
fed Purina diet for 20 weeks and then switched to either milk protein diet for
a further 8 weeks exhibited a decrease in tumour burden as compared to those
animals fed the Purina diet continuously. Body weights were similar in all
dietary groups. In conclusion, a whey protein diet appears to significantly
influence the development of chemically induced colon tumours and the
short-term survival of mice.
CLIN INVEST MED, 12: 343-349, 1989
7-
THE INFLUENCE OF DIETARY WHEY PROTEIN ON TISSUE
GLUTATHIONE
AND THE DISEASES OF AGING
Gustavo
Bounous1,2, Francine Gervais1,3, Victor Amer1,3,
Gerald Batist3, and Phil Gold1,3
The
Montreal General Hospital Research Institute1 and McGill University, Departments of Surgery2,
and Medicine3
ABSTRACT – This study compared the
effects of a whey-rich diet (20 g / 100 g diet), with that of Purina mouse chow
or casein-rich diet (20 g / 100 g diet), on the liver and heart glutathione
content and on the survival of old male C57BL / 6 NIA mice. The study was
performed during a limited observation period of 6.3 months. In mice fed the
whey protein-rich diet between 17 months and 20 months of age, the heart tissue
and liver tissue glutathione content were enhanced above the corresponding
values of the casein diet-fed and Purina-fed mice. Mice fed the whey protein
diet at the onset of senescence, exhibited increased longevity as compared to
mice fed Purina mouse chow over the 6.3 month observation period extending from
the age of 21 months (corresponding to a human age of 55 years) to 26-27 months
of age (corresponding to a human age of 80 years), during which time 55%
mortality was observed. The corresponding mean survival time of mice fed the
defined casein diet is almost identical to that of Purina-fed controls. Body
weight curves were similar in all three dietary groups. Hence, a whey protein
diet appears to enhance the liver and heart glutathione concentration in aging
mice and to increase longevity over a 6.3 month observation period.
CLIN INVEST MED, 12: 154-61, 1989
ROLE
OF GLUTATHIONE
G.
Bounous, G. Batist, P. Gold
Montreal
General Hospital, Quebec
ABSTRACT – The spleen cells immune
response to sheep red blood cells of C3H/HeJ mice fed a 20 g whey protein/100 g
diet is substantially higher than that of mice fed an equivalent casein diet of
similar nutritional efficiency. The present study indicates that the observed
immunoenhancing effect of the whey protein mixture is dependent on the overall
amino acid pattern resulting from the contribution of all its protein
components. Whey protein contains substantially more cysteine than casein.
Dietary cysteine is considered to be a rate limiting substrate for the
synthesis of glutathione which is necessary for lymphocyte proliferation. Our
studies show that enhancement of host humoral immune response is associated
with greater and more sustained production of splenic glutathione during the
antigen driven clonal expansion of the lymphocyte in whey protein fed mice in
comparison to mice fed the equivalent casein or the cysteine-enriched casein
diet. Hence the efficiency of dietary cysteine in inducing supernormal
glutathione levels is greater when it is delivered in the whey protein than as
free cysteine. Administration of S-(n-butyl) homocysteine sulfoximine, which
reduces splenic glutathione level by half, produces a 4-5 fold drop in the
humoral immune response of whey protein diet-fed mice. This is further evidence
of the important role of glutathione in the immunoenhancing effect of dietary
whey protein.
CLINICAL AND INVESTIGATIVE MEDICINE, VOL. 11,.NO. 4,.PP 271-278,. 1988.
9- THE IMMUNOENHANCING PROPERTY OF DIETARY WHEY PROTEIN CONCENTRATE.
Gustavo Bounous1,2, Patricia A.L. Kongshavn1,3 and Phil Gold1,4 - 1The Montreal General Hospital Research Institute, 2[)epartments of Surgery, 3Physiology, and 4Medicine, McGill University, Montreal, Quebec - (ORIGINAL MANUSCRIPT SUBMITTED OCTOBER 22, 1987: ACCEPTED IN REVISED FORM JANUARY 25, 1988)
ABSTRACT - The plaque-forming cell
response to sheep red blood cells was found to be enhanced in mice fed a
formula diet containing 20 g lactalbumin /100 g diet in comparison to mice fed
equivalent formula diets of similar nutritional efficiency containing 20 g /
100 g diet of either casein, soy, wheat or corn protein, egg albumin, beef or
fish protein, Spirulina maxima, or Scenedesmus protein, or Purina
mouse chow. This effect was manifest after 2 weeks and persisted for at
least 8 weeks of dietary treatment. Mixing lactalbumin with either casein or
soy protein in a 20 g protein / 100 g diet formula significantly enhanced the
immune response in comparison to that of mice fed diets containing 20% soy
protein or casein.
CLIN INV MED, 11: 213-217, 1988
10- MECHANISM OF ALTERED B-CELL RESPONSE INDUCED BY CHANGES IN DIETARY PROTEIN TYPE IN MICE
G. Bounous, N. Shenouda,* P.A.L. Kongshavn† and D.G. Osmond* Department of Surgery, Centre Hospitalier Universitaire, Sherbrooke, Quebec, Canada, J1H 5N4; *Department of Anatomy, McGill University, Montreal, Quebec, Canada, H3A 2B2; and †Department of Physiology, McGill University, Montreal, Quebec, Canada, H3A 2B2.
ABSTRACT – The effect of 20 g/100 g dietary
lactalbumin (L) or casein (C) diets or a nonpurified (NP) diet on the immune
responsiveness of C57B1/6J, C3H/HeJ and BALB/cJ mice has been investigated by
measuring the response to the T cell-independent antigen, TNP-Ficoll. To
investigate the possible influence of dietary protein type on the supply of B
lymphocytes, bone marrow lymphocyte production has been examined by a
radioautographic assay of small lymphocyte renewal and an immuno-fluorescent
stathmokinetic assay of pre-B cells and their proliferation. The humoral
response of all mice fed the L diet was found to be higher than that of mice
fed the C diet or non purified diet. A similar pattern of dietary protein
effect in (CBA/N x DBA/2J) F1 mice carrying the xid defect
was observed following challenge with sheep red blood cells (SRBC). An even
greater enhancing effect of dietary L was noted in normal (DBA/2J x CBA/N) F1
mice after immunization with SRBC, but in contrast, the normal large-scale
production of B lymphocytes in mouse bone marrow was independent of the type of
dietary protein. Dietary protein type did not affect blood level of minerals
and trace metals. The free plasma amino acid profile essentially conformed to
the amino acid composition of the ingested protein, suggesting that the changes
in plasma amino acid profile might be a crucial factor in diet-dependent
enhancement or depression of the B-cell response. The findings indicate that
the observed effects of altered dietary protein type on humoral immune
responsiveness are not exerted centrally on the rate of primary B-lymphocyte
production in the bone marrow, but may reflect changes either in the functional
responsiveness of the B lymphocytes themselves or in the processes leading to
their activation and differentiation in the peripheral lymphoid tissues.
INDEXING KEY WORDS: DIET – PROTEIN – IMMUNITY
– B-CELL RESPONSE - MICE --
J. NUTR. 115: 1403-1408, 1985.
12- DIFFERENTIAL EFFECT OF DIETARY PROTEIN TYPE ON THE B-CELL AND T-CELL IMMUNE RESPONSES IN MICE
Gustavo Bounous and Patricia A.L. Kongshavn* Centre Hospitalier Universitaire, Sherbrooke, Québec, Canada, J1H 5N4 and *Montreal General Hospital Research Institute and Department of Physiology, McGill University, Montreal, Quebec, Canada, H3G 1Y6
ABSTRACT – The effect of 20 g/100 g
diet of lactalbumin (L), casein (C), soy (S) and wheat (W) protein on the
immune responsiveness of C3H/HeN mice has been investigated by measuring the
humoral immune response to the T cell-independent antigen, TNP-Ficoll. The
humoral immune response of mice fed the L diet was found to be higher than that
of mice fed the C, S and W diets. On the other hand, delayed-type
hypersensitivity, and splenic cell mitogen responses to phytohemagglutinin and
concanavalin A did not differ among mice fed the various diets. Similarly, the
type of diet did not appear to influence host resistance to Salmonella
typhymurium. It is postulated that the type of protein in the diet
influences directly the intrinsic capacity of the B lymphocytes to respond to
an immunogenic stimulus.
Indexing Key
Words: diet * protein * immunity * mice -
J. NUTR. 113: 1415-1421, 1983
G. Bounous, L. Létourneau and P.A.L. Kongshavn† Centre hospitalier universitaire, Sherbrooke, Quebec, Canada; J1H 5N4 and †Montreal General Hospital Research Institute and Department of Physiology, McGill University, Montreal, Quebec, Canada, H3G 1Y6.
ABSTRACT – The
effect of graded amounts of dietary lactalbumin (L), casein (C), soy (S), wheat
(W) protein and Purina rodent chow
(stock diet) on the immune responsiveness of C3H/HeN mice has been investigated
by measuring the specific humoral immune response to sheep red blood cells (SRBC),
and horse red blood cells (HRBC) as well as the nonspecific splenic cell
responsiveness to phyto-hemagglutinin (PHA) and concanavalin A (Con A) after
stimulation with Myco-bacterium bovis, strain BCG. The
nutritional efficiency of these diets was normal and similar. The immune
response of mice fed the L diets, was found to be almost five times higher than
that of mice fed the corresponding C diets. The humoral immune response of mice
fed C, S, and W diets was substantially lower than that of mice fed stock diet,
whereas that of mice fed L diet was higher. The above-described immune effect
of all tested proteins was obtained at 20 g/100 g concentration with no further
increments with 30- and 40 g/100 g protein in the diet. Mitogen responsiveness
to PHA and Con A in L diet-fed mice was only slightly higher than that of C
diet-fed mice. Little difference in immune responses was noted among mice fed
C, S or W protein diets. The principal factor responsible for the observed
immune effect does not appear to be the availability or concentration of single
essential amino acids but rather the composite effect of the specific amino
acid distribution in the protein.
MINERVA DIETOL GASTROENTEROL
35(4): 241-5, 1989
14-
CHANGES IN BILIARY SECRETORY IMMUNOGLOBULINS A IN MICE FED
WHEY
PROTEINS
Costantino
AM, Balzola F, Bounous G.
A whey protein diet has been shown to
enhance splenic immune response to sheep red blood cells (SBRC) in mice. This
study was designed to investigate the influence of the type of dietary protein
on the biliary secretory IgA. A/J mice were fed defined formula diets
containing either 20% whey protein, or 20% casein. Another group was fed Purina
mouse chow. After 3 weeks of dietary treatment the body weight of each mouse
was recorded and the gall-bladder was removed and its whole content analyzed by
ELISA to determine S-IgA secretion. Body weight curves were similar in all
dietary groups; higher biliary levels of S-IgA appeared in the whey protein fed
mice than in the casein (p less than 0.025) or purine (p less than 0.025) fed
mice. Dietary protein type may have a direct influence on the immune response
in the gastrointestinal tract, without affecting body weight.
OXIDATIVE STRESS,
CELL ACTIVATION AND VIRAL INFECTION C. PASQUIER ET AL. (EDS) 1994
BIRKHÄUSER VERLAG BASEL/SWITZERLAND
15- PLACE
FOR AN ANTIOXIDANT THERAPY IN HUMAN IMMUNODEFICIENCY
VIRUS
(HIV) INFECTION
S.
Baruchel1,2 G. Bounous2, P. Gold2
1McGill
University, Dept. of Pediatrics; McGill AIDS Centre. Montreal. Qc. H3H 1P3,
Canada
2 McGill University, Dept of Medicine;
McGill AIDS Centre. Montreal. Qc. H3G 1A4, Canada
SUMMARY - Oxidative stress, a known
activator of HIV replication in vitro, has a potential role as a cofactor
of HIV disease progression. Arguments supporting the role of oxidative stress
as a cofactor in HIV activation are summarized in this review. The role of
intracellular antioxidants such as glutathione (GSH), and drugs and
nutriceutical
agents
promoting GSH synthesis, are discussed. The review also includes the early
results of nutritional interventions based on a diet enriched with IMMUNOCAL ,
a whey protein concentrate prepared in a proprietary manner.
J. Nutr. 112:1747-1755, 1982. - Reprinted from THE JOURNAL
OF NUTRITION
Vol. 112, no. 9, September 1982 © The American Institute of
Nutrition 1982
16- INFLUENCE OF DIETARY PROTEINS ON
THE
IMMUNE SYSTEM OF MICE1
G.
Bounous2o and PAL Kongshavn†
oCentre Hospitalier Universitaire,
Sherbrooke, Quebec, Canada, J1H 5N4 and †Montreal General Hospital Research Institute
and Department of Physiology, McGill University, Montreal, Quebec, Canada, H3G
1Y6
ABSTRACT The effect of graded amounts
of dietary laetalbumin (L) and casein (C) hydrolyzates on the immune
responsiveness of C3H/HeN and DBA/2 strain mice has been investigated by
measuring both the specific humoral immune response to sheep red blood cells
(SRBC) and the nonspecific splenic cell responsiveness to phytohemagglutinin,
concanavalin A and Escherichia coli lipopolysaccharide after stimulation
with Mycobacteriurn bovis, strain BCG. The nutritional efficiency
of these diets was similar at both 12 and 28% amino acid levels. The immune
responses of mice fed the L diets were found to be significantly greater than
those of mice fed the corresponding C diets, especially at the 28% level.
Furthermore in the mice fed L diet, increasing the concentration of amino acid
in the diet from 12 to 28% greatly enhanced immune responsiveness by both
parameters measured. In the C-fed mice, a comparable enhancement of mitogen
responsiveness with increasing amino acid level of diet was seen, but there was
no change in the humoral immune response. The enhancement of immune
responsiveness observed in mice fed the 28% L diet was moderately reduced by
the addition of phenylalanine to the diet, indicating that the lower level of
this amino acid in the L protein may be of some significance. These dietary
effects on immune responsiveness were remarkably similar in both mouse strains
tested.
THE JOURNAL OF INFECTIOUS DISEASES, 144: 281, 1981
17- INFLUENCE
OF DIETARY LACTALBUMIN HYDROLYSATE ON THE IMMUNE
SYSTEM
OF MICE AND RESISTANCE TO SALMONELLOSIS
G.
Bounous, M.M. Stevenson*, P.A.L. Kongshavn†
Centre
hospitalier universitaire, Sherbrooke, Quebec, Canada; *Montreal General
Hospital Research Institute and †McGill University, Montreal, Quebec, Canada
ABSTRACT – In the present study we
investigated the effect of four weeks of treatment with a diet containing
lactalbumin hydrolysate (LAH: Nestlé, Vevey, Switzerland) on the immune
response of C3H/HeN mice. Our data indicate that it was possible to increase
the level of this type of protein in the diet above the minimum requirement
(12% LAH) and thus produce augmented humoral immune responsiveness and
resistance to salmonellosis.
JOURNAL OF APPLIED PHYSIOLOGY, 87: 1381-1385, 1999
18-
THE EFFECT OF SUPPLEMENTATION WITH A CYSTEINE DONOR ON
MUSCULAR
PERFORMANCE
LC
Lands, MD, PhD*†, VL Grey, PhD†‡, AA Smountas, BSc*
*Division
of Respiratory Medicine, † Department of Pediatrics, ‡Department of
Biochemistry, McGill University
Health
Centre-Montreal Children’s Hospital, Montreal, Quebec, Canada
ABSTRACT: Oxidative stress contributes
to muscular fatigue. Glutathione (GSH) is the major intracellular antioxidant,
whose biosynthesis is dependent upon cysteine availability. We hypothesized
that supplementation with a whey-based cysteine donor (Immunocal (HMS90))
designed to augment intracellular GSH, would enhance performance. Twenty
healthy young adults (10 m) were studied pre- and 3 months post-supplementation
with either Immunocal (20 gm/day) or casein placebo. Muscular performance was
assessed by whole leg isokinetic cycle testing, measuring Peak Power and 30-sec
Work Capacity. Lymphocyte GSH was used as a marker of tissue GSH. There were no
baseline differences (age, ht, wt, % ideal wt, Peak Power, 30-sec Work Capacity).
Follow-up data on 18 subjects (9 Immunocal, 9 placebo) were analyzed. Both Peak
Power (meanse: 133.5%, p0.02) and 30-sec Work Capacity (133.7%,
p0.03)
increased significantly in the Immunocal group, with no change (29.0
and 19.3%)
in the placebo group. Lymphocyte GSH also increased significantly in the
Immunocal group (35.511.04%, p0.02) with no change in the placebo
group (-0.99.6%). This is the first study to
demonstrate that prolonged supplementation with a product designed to augment
antioxidant defenses resulted in improved volitional performance.
ACCEPTED FOR PUBLICATION IN “CHEST”
19- TREATMENT
OF OBSTRUCTIVE AIRWAY DISEASE WITH A CYSTEINE
DONOR
PROTEIN SUPPLEMENT: A CASE REPORT
Bryce
Lothian, MD*, Vijaylaxmi Grey, PhD*†, R. John Kimoff, MD‡, Larry Lands, MD,
PhD*§
*Department
of Pediatrics, †Department of Biochemistry, §Division of Respiratory Medicine,
McGill University
Health
Centre-Montreal Children’s Hospital, Montreal, Quebec, Canada
‡Division
of Respiratory Medicine, McGill University Health Centre-Royal Victoria
Hospita, Montreal, Quebec Canada.
ABSTRACT:Oxidant/antioxidant imbalance
can occur in obstructive airways disease, as a result of ongoing inflammation.
Glutathione plays a major role in pulmonary antioxidant protection. As an
alternative or complement to anti-inflammatory therapy, augmenting antioxidant
protection could diminish the effects of inflammation. We describe a case of a
patient with obstructive lung disease, responsive to corticosteroids, with low
whole blood glutathione levels. Following one month of supplementation with a
whey-based oral supplement, designed to provide glutathione precursors, whole
blood glutathione levels and pulmonary function significantly and dramatically
increased. The potential for such supplementation in pulmonary inflammatory
conditions deserves further study.
PR514
20- TREATMENT OF CHRONIC HEPATITIS USING
WHEY
PROTEIN (NON-HEATED)
A.
Watanabe, K. Higuchi, K. Okada, Y. Shimizu, Y. Kondo* and H. Kohri*
Department
of Internal Medicine, Toyama Medical and Pharmaceutical University, Toyama,
Japan, and * Otsuka
Pharmaceutical
Factory, Inc., Nutrition Research Institute, Tokushima. Japan.
In an open study, the clinical efficacy
of whey protein (Immunocal: cysteine content; 7.6-fold that of casein) isolated
from fresh milk and purified without being heated was evaluated based on liver
function test, immunological parameters, plasma or lymphocyte GSH
concentrations and hepatitis virus markers in 25 patients with chronic
hepatitis B or C. Immunocal (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 given for 2 weeks prior to the start of -supplement
with Immunocal food (induction period) and for 4 weeks after the end
(follow-up period). The effects of Immunocal food on various clinical
parameters were examined at 4-week intervals for 18 weeks to evaluate the
efficacy of Immunocal. As a result, serum ALT activity decreased in 6 of 8
patients with chronic hepatitis B 12 weeks after the start of supplement with Immunocal
food. Plasma GSH concentrations were increased in 5 of the 8 patients. Serum .
concentrations of lipid peroxides significantly decreased 8 weeks after
Immunocal food. Serum IL-2 levels began to increase 8 weeks and remained high
even after supplement with Immunocal -food had ended. Furthermore, NK activity
was significantly increased. However, an item correlating with reduced serum
ALT activity could not be clarified. In 17 patients with chronic hepatitis C,
there wore no significant Immunocal-related changes in liver function test or
immunological parameters. These findings suggest that long-term supplement with
Immunocal alone may be effective for patients with chronic hepatitis B, and a
further clinical study that long-term combination therapy with Immunocal and
other agents including interferon may be effective for those with chronic
hepatitis C should be performed.
Anticancer Research 20: 4785-4792, 2000.
21- WHEY
PROTEIN CONCENTRATE (WPC) AND GLUTATHIONE MODULATION
IN
CANCER TREATMENT
Gustavo
Bounous, M.D., F.R.C.S. (C)
ABSTRACT - The glutathione (GSH)
antioxidant system is foremost among the cellular protective mechanisms.
Depletion of this small molecule is a common consequence of increased formation
of reactive oxygen species during increased cellular activities. This phenomenon
can occur in the lymphocytes during the development of the immune response and
in the muscular cells during strenuous exercise. It is not surprising that so
much research has been done, and is still being done on this small tripeptide
molecule. Whey protein concentrate has been shown to represent an effective and
safe cysteine donor for GSH replenishment during GSH depletion in immune
deficiency states. Cysteine is the crucial limiting amino acid for
intracellular GSH synthesis. Animal experiments showed that the concentrates of
whey proteins also exhibit anti-carcinogenesis and anticancer activity. They do
this via their effect on increasing GSH concentration in relevant tissues, and
may have anti-tumor effect on low volume of tumor via stimulation of immunity
through the GSH pathway. It is considered that oxygen radical generation is
frequently a critical step in carcinogenesis, hence the effect of GSH on free
radicals as well as carcinogen detoxification, could be important in inhibiting
carcinogenesis induced by a number of different mechanisms. Case reports are
presented which strongly suggest an anti-tumor effect of a whey protein dietary
supplement in some urogenital cancers. This non toxic dietary intervention,
which is not based on the principles of current cancer chemotherapy, will
hopefully attract the attention of laboratory and clinical oncologists.
ACCEPTED FOR PUBLICATION IN NUTRITION AND CANCER, VOL 38, ISSUE
#2
22- ENHANCING EFFECT OF PATENTED WHEY PROTEIN ISOLATE (IMMUNOCAL ) ON THE CYTOTOXICITY OF ANTI-CANCER DRUG
Wayne
Y. Tsai, Wen-Huei Chang, Ching-Hsein Chen, and Fung-Jou Lu
Department
of Biochemistry, College of Medicine National Taiwan University, Taipei,
Taiwan, R.O.C.
ABSTRACT – To determine the enhancing
effect of a whey protein isolate on the cytotoxicity of a potential anti-cancer
drug. baicalein, human hepatoma cell line HepG2 was assigned to grow in
different media for four days, followed by the investigation of cell growth and
apoptosis. Excluding the control group with normal medium, other three
treatment media included whey protein isolate (marketed as Immunocal )
medium, baicalein medium, and combined medium containing both Irnmunocal and baicalein. MTT assay indicated that cells
grew in combined medium had a significantly lower survival rate compared to the
cells grew in baicalein medium; in contrast, for the cells grew in Immunocal group, there was no significant difference on
survival rate. In the investigation of apoptosis. compared to the cells in
baicalein medium, cells in combined medium showed a higher phosphatidylserine
exposure, lower rnitochondrial transmembrane potential and nearly 13 times more
cells were detected undergoing apoptosis. We also demonstrated that Immunocal was able to reduce glutathione in HepG2 by 20%
to 40% and regulated the elevation of glutathione, which was in response to
baicalein. In conclusion, Immunocal
seemed to enhance the cytotoxicity of
baicalein by inducing more apoptosis, this increase in apoptotic cells may be
in association with the depletion of GSH in HepG2. This is the first study to
demonstrate, in vitro, that Immunocal
may function as an adjuvant in cancer
treatments.
OXIDATIVE STRESS IN CANCER,
AIDS, AND NEURODEGENERATIVE DISEASES
– LUC MONTAGNIER ET AL.,
(ED.) MARCEL
DEKKER INC., NEW YORK: 447-461, 1998
23-
NUTRICEUTICAL MODULATION OF GLUTATHIONE WITH A HUMANIZED
NATIVE
MILK SERUM PROTEIN ISOLATE, IMMUNOCAL
:
APPLICATION
IN AIDS AND CANCER.
S.
Baruchel*, G. Viau*, R. Olivier**, G. Bounous , M.A. Wainberg *
*McGill
University – Montreal Children’s Hospital Research Institute, Montreal, Quebec,
Canada, **Pasteur Institute Paris, France, Montreal General Hospital, Montreal, Quebec,
Canada, *Jewish General Hospital, Lady
Davis Institute, Montreal, Quebec, Canada.
ABSTRACT – The biological activity of
the proteins isolated from cow’s milk in Immunocal depends on the preservation of those labile
proteins which share with the predominant human milk proteins the same
extremely rare glutathione (GSH)-promoting components. Cellular GSH depletion
has been implicated in the pathogenesis of a number of degenerative conditions
and disease states including Parkinson’s, Alzheimer’s, arteriosclerosis,
cataracts, cystic fibrosis, malnutrition, aging, AIDS, and cancer.
This newly discovered nutriceutical
modulation of GSH by the use of humanized native milk serum protein isolate of
bovine origin in AIDS and cancer may well find other applications in disease
where oxidative stress and pathology of GSH metabolism are largely implicated.
In a pilot study, this type of whey protein concentrate was found to be well
tolerated in children with AIDS and wasting syndrome and was found associated
with an improvement of the nutritional status of the patient. Moreover, the GSH
promoting activity on the peripheral blood lymphocyte of this protein
concentrate was validated in patients with initial low GSH levels. Extensive
pharmaco-epidemiological study of GSH metabolism and standardized methods of
measurement of intracellular GSH applicable in clinical trials are needed in
order to better define the clinical application of this new type of therapy.
ANTICANCER RESEARCH 23: 1411-1416 (2003)
24- THE ANTIOXIDANT SYSTEM
G.
Bounous and J. H. Molson
Research
and Development Department Immunotec Research Ltd., Vaudreuil-Dorion, Quebec,
Canada.
ABSTRACT – The glutathione (GSH)
antioxidant system is the principal protective mechanism of the cell and is a
crucial factor in the development of the immune response by the immune cells.
Experimental data demonstrate that a cysteine-rich whey protein concentrate
represents an effective cysteine delivery system for GSH replenishment during
the immune response. Animal experiments showed that the concentrates of whey
protein also exhibit anticancer activity. They do this via the GSH pathway, the
induction of p53 protein in transformed cells and inhibition of
neoangiogenesis.
CAN J CARDIOL VOL 19, NO 10, SEPTEMBER 2003.
25-
MILK WHEY PROTEIN DECREASES OXYGEN FREE RADICAL
PRODUCTION
IN A MURINE MODEL OF
CHRONIC
IRON-OVERLOAD CARDIOMYOPATHY
WJ
Bartfay, MT Davis, JM Medves, S Lugowski
ABSTRACT – Chronic iron overload is a
major cause of organ failure worldwide, but its pathogenesis remains to be
elucidated.
To examine in an
experimental murine model of iron-overload cardiomyopathy the relation between
milk whey protein and, first, the production of reactive oxygen free radical
species and, second, antioxidant reserve status.
B6D2F1 mice were
randomly assigned to four treatment groups (n=8 per treatment group): placebo
control; iron only; whey only; and iron with whey. Reactive oxygen free radical
species in the heart were quantified by the cytotoxic aldehydes malondialdehyde
(MDA), 4-hydroxy-nonenal (HNE) and hexanal, while antioxidant reserve status
was quantified by glutathione (GSH) and glutathione peroxidase (GPx) activity
in the heart tissue.
Significantly
decreased concentrations (pmol/100 mg wet weight tissue) of MDA (2468
± 261), HNE (912 ± 38) and hexanal
(5385 ± 927) were observed in the heart tissue of the group receiving iron with
whey, in comparison with the iron-only treatment group (MDA 9307 ± 387, HNE
1416 ± 157, hexanal 14,874 ± 2955; P<0.001). Significantly increased GPx
(141 ± 38 IU/L) and GSH (521 ± 136 IU/L) activity were observed in mice
receiving iron with whey, in comparison with mice receiving iron only (GPx 100
± 10 IU/L, GSH 446 ± 33 IU/L; P<0.001).
Mice receiving iron treatments with
whey supplementation had significantly lower concentrations of cytotoxic
aldehydes and significantly higher cardiac levels of GPx and GSH activity than
did iron-only treated mice. Additional basic research is warranted to examine
the exact mechanisms by which milk whey protein protects the heart.
ANTICANCER RESEARCH 24: 553-554 (2004)
26-
MOLECULAR PATHOGENESIS AND PREVENTION OF PROSTATE CANCER
G.
Bounous, D. Beer
ABSTRACT –
Studies in laboratory animals indicate inhibition of chemically-induced
carcinoma by cystine-rich diets enhancing the cysteine-GSH antioxidant system.
The progression of carcinoma of the prostate is also inhibited by these diets,
which were later found to raise the level of GSH in the prostate epithelium of
man. New data presented at the July 13, 2003 meeting of the American
Association for Cancer Research
indicates that higher levels of total cysteine in plasma may predict a reduced
risk for breast cancer. This prospective investigation was conducted among
32,000 women in the Nurses Health study. The previously reported prostate
cancer data appears then not to be strictly gender-related as the antioxidant
role of the cysteine – GSH system may also apply to breast cancer prevention.
JOURNAL OF CYSTIC FIBROSIS,
VOL 2, ISSUE 4, DECEMBER 2003
27-
IMPROVED GLUTATHIONE STATUS IN YOUNG ADULT PATIENTS WITH
CYSTIC
FIBROSIS SUPPLEMENTED WITH WHEY PROTEIN
V
Greya, SR Mohammedb, AA Smountasb, R Bahloolb,
LC Landsb
aThe Department of Pathology and Molecular Medicine, McMaster
Division, Hamilton Health Sciences, Hamilton,
Ontario,
Canada
bThe
Department of Respiratory Medicine, McGill University Medical Center, Montreal
Children’s Hospital,Montreal,
Quebec,
H3H 1P3, Canada
ABSTRACT – Background:
The lung disease of cystic fibrosis is associated with a chronic inflammatory
reaction and an over abundance of oxidants relative to antioxidants.
Glutathione functions as a major frontline defense against the build-up of
oxidants in the lung. This increased demand for glutathione (GSH) in cystic
fibrosis may be limiting if nutritional status is compromised. We sought to
increase glutathione levels in stable patients with cystic fibrosis by
supplementation with a whey-based protein. Methods: Twenty-one patients
who were in stable condition were randomly assigned to take a whey protein
isolate (Immunocal, 10 g twice a day) or casein placebo for 3 months.
Peripheral lymphocyte GSH was used as a marker of lung GSH. Values were
compared with nutritional status and lung
parameters. Results: At baseline
there were no significant differences in age, height, weight, percent ideal
body weight or percent body fat. Lymphocyte GSH was similar in the two groups.
After supplementation, we observed a 46.6% increase from baseline (P<0.05)
in the lymphocyte GSH levels in the supplemented group. No other changes were
observed. Conclusion: The results show that dietary supplementation
with a whey-based product can increase glutathione levels in cystic fibrosis.
This nutritional approach may be useful in maintaining optimal levels of GSH
and counteract the deleterious effects of oxidative stress in the lung in
cystic fibrosis.
MED. SCI. SPORTS EXERC., VOL. 37, NO. 9, PP. 1468-1473,
2005.
28-
EFFECTS OF CYSTEINE DONOR SUPPLEMENTATION ON EXERCISE-
INDUCED
BRONCHOCONSTRICTION
JM
Baumann, KW Rundell, TM Evans, AM Levine
American
College of Sports Medicine. Marywood University, Human Performance Laboratory,
Scranton, PA
ABSTRACT – Purpose:
Reactive oxygen/nitrogen species (ROS/RNS) in resident airway cells may be
important in bronchoconstriction following exercise. Glutathione (GSH) is a
major lung antioxidant and could influence pathological outcomes in individuals
with exercise-induced bronchoconstriction (EIB). This study examined the
effects of supplementation with undenatured whey protein (UWP) in subjects
exhibiting airway narrowing following eucapnic voluntary hyperventilation
(EVH), a surrogate challenge for diagnosis of EIB. UWP is a cysteine donor that
augments GSH production. Methods: In a randomized, double-blind,
placebo-controlled study, 18 EIB-positive subjects (age: 25.2
9.01 yr; weight: 77.3 18.92 kg; height: 1.7
0.09 m) with post-EVH falls of 10% in FEV received 30 g UWP (TX) or
casein placebo (PL)/d. Subjects performed 6-min EVH challenges before and after
4 and 8 wk of supplementation. Exhaled nitric oxide (eNO) was measured serially
before spirometry and at 1-wk intervals. Spirometry was performed pre-and 5,
10, and 15 min postchallenge. Results:
Subjects exhibited significant mean
improvement in postchallenge falls in FEB from 0 wk (-2.6 12.22%) with TX at 4 (-18.9 12.89%, P0.05) and 8 wk (-16.98 11.61%, P 0.05) and significant mean reduction
in post-EVH peak falls in FEF from 0 wk (-40.6 15.28%) with TX at 4 (-33.1 17.11%, P 0.01) and 8 (-29.7 17.42%, P0.05) wk. No changes in FEV or FEF were observed in the PL
group at any time point. Mean eNO for PL and TX groups at 0, 4, and 8 wk (46.8 31.33, 46.5 35.73, 49.3 37.12 vs 35.2 26.87, 29.1 17.26, 34.7 21.11 ppb, respectively) was not
significantly different. Conclusions: UWP may augment pulmonary
antioxidant capacity and be therapeutically beneficial in individuals
exhibiting EIB, as postchallenge pulmonary function improved with
supplementation. The lack of significant change in eNO suggests that the
pulmonary function improvements from UWP supplementation are independent of
eNO.
PHIL. TRANS. R. SOC. B. 360, 2355-2372 (2005).
29- OXIDATIVE STRESS AND AGEING: IS AGEING A CYSTEINE
DEFICIENCY
SYNDROME?
W.
Dröge,
Division
of Redox Physiology and Aging Research, Deutsches Krebsforschungszentrum,
Im
Neuenheimer Feld 280, 69120 Heidelberg, Germany
ABSTRACT –
Reactive oxygen species (ROS) are constantly produced in biological tissues and
play a role in various signaling pathways. Abnormally high ROS concentrations
cause oxidative stress associated with tissue damage and dysregulation of
physiological signals. There is growing evidence that oxidative stress
increases with age. It has also been shown that the life span of worms, flies
and mice can be significantly increased by mutations, which impede the insulin
receptor signaling cascade. Molecular studies revealed that the
insulin-independent basal activity of the insulin receptor is increased by ROS
and downregulated by certain antioxidants. Complementary clinical studies
confirmed that supplementation of the glutathione precursor cysteine decreases
insulin responsiveness in the fasted state. In several clinical trials,
cysteine supplementation improved skeletal muscle functions, decreased the body
fat/lean body mass ratio, decreased plasma levels of the inflammatory cytokine
tumour necrosis factor (TNF-), improved immune functions, and
increased plasma albumin levels. As all these parameters degenerated with age,
these findings suggest: (i) that loss of youth, health and quality of life may
be partly explained by a deficit in cysteine and (ii) that the dietary
consumption of cysteine is generally suboptimal and everybody is likely
to have a cysteine deficiency sooner or later.
ANTIOXIDANTS & REDOX SIGNALING, 10:661-675 (2008)
30– ABERRANT INSULIN RECEPTOR SIGNALING AND AMINO ACID
HOMEOSTASIS
AS
A MAJOR CAUSE OF OXIDATIVE STRESS IN AGING
W.
Dröge a) R.
Kinscherf b).
a)
Dept.
Research & Development, Immunotec Inc., Vaudreuil, Quebec, Canada
b)Dept.
Anatomy & Developmental Biology, University of Heidelberg, Mannheim,
Germany
ABSTRACT – The mechanisms leading to
the increase in free-radical-derived oxidative stress in “normal aging”
remained obscure. Here we present our perspective on studies from different
fields which reveal a previously unnoticed vicious cycle of oxidative stress.
The plasma cysteine concentrations during starvation in the night and early
morning hours (the postabsorptive state) decreases with age. This decrease
is associated with a decrease in tissue concentrations of the cysteine derivative
and quantitatively important antioxidant glutathione. The decrease in cysteine
reflects changes in the autophagic protein catabolism which normally ensures
free amino acid homeostasis during starvation. Autophagy is negatively
regulated by the insulin receptor signaling cascade, which is enhanced by
oxidative stress in the absence of insulin. This synopsis of seemingly
unrelated processes reveals a novel mechanism of progressive oxidative stress
in which decreasing antioxidant concentrations and increasing basal (postabsorptive)
insulin receptor signaling activity compromise not only the autophagic protein
catabolism but also the activity of FOXO transcription factors, i.e. two
functions which were found to have an impact on lifespan in several animal
models of aging. In addition, the aging-related decrease in glutathione level
is likely to facilitate certain “secondary” disease-related mechanisms of
oxidative stress. Studies on cysteine supplementation show therapeutic promise.
ANTIOXIDANTS & REDOX SIGNALING, 10:395-402, (2008)
31–CYSTEINE-RICH
PROTEIN REVERSES WEIGHT LOSS IN LUNG CANCER
PATIENTS
RECEIVING CHEMOTHERAPY OR RADIOTHERAPY
R.
Tozer, a) P. Tai, b) W. Falconer, c) T. Ducruet, d) A. Karabadjian, e) G. Bounous, f)
J.
Molson f) and W. Dröge f)
a)
Hamilton
Regional Cancer Centre, Hamilton, Ontario, Canada. b)
Radiation Oncology, Allan Blair Cancer Center, Regina, Saskatchewan, Canada, c) Cancer Nutrition & Rehabilitation
Program, Dept. of Oncology, McGill University,
Montreal,
Quebec. Canada, d) Boreal Primum Inc., Montreal, Quebec,
Canada e)Medscope Communications Inc., St.
Laurent, Quebec, Canada f) Immunotec Research Ltd. Vaudreuil, Quebec
Canada.
ABSTRACT – Oxidative stress plays a
role in the tumor-cytotoxic effect of cancer chemotherapy and radiotherapy and
also in certain adverse events. In view of these conflicting aspects, a
double-blind trial over 6 months has been performed to determine whether a
cysteine-rich protein (IMN1207) may have a positive or negative effect on the
clinical outcome if compared with casein, a widely used protein supplement low
in cysteine. Sixty-six patients with Stage IIIB-IV non-small cell lung cancer
were randomly assigned to IMN1207 or casein. Included were patients with a
previous involuntary weight loss of ≥3%,
Karnofsky status ≥70, and an
estimated survival of > 3 months. Thirty-five lung cancer patients remained
on study at six weeks. Overall compliance was not different between treatment
arms (42-44% or 13g/day). The patients treated with the cysteine-rich protein
had a mean increase of 2.5% body weight while casein-treated patients lost 2.6%
(P=0.049). Differences in secondary end points included an increase in
survival, hand grip force and quality of life. Adverse events were mild or
moderate. Further studies will have to show whether the positive clinical
effects can be confirmed and related to specific parameters of oxidative stress
in the host.
IMMUNOLOGY. 172:151-156, (1986)
32–GLUTATHIONE
AUGMENTS THE ACTIVATION OF CYTOTOXIC T
LYMPHOCYTES
IN VIVO
W.
Dröge, Christiane
Pottmeyer-Gerber, Heike Schmidt, and Sabine Nick
Institut
für
Immunologie und Genetik, Deutsches Krebsforschungszentrum, Heidelberg,
ABSTRACT – The
activation of cytotoxic T lymphocytes (CTL) in vivo was found to be
augmented by glutathione if injected i.p. in the late phase but not in the
early phase of the response. The effect of glutathione possibly resembles the
augmenting effect of 2-mercaptoethanol in lymphocyte cultures.
JANA VOL. 11, NO. 1, (2008)
33-ORAL
TOLERABILITY OF CYSTEINE-RICH WHEY PROTEIN ISOLATE IN AUTISM
–
A PILOT STUDY
Janet
K. Kern a), Bruce D. Grannemann, a) Jimmy Gutman, b) Muadhukar H. Trivedi a)
a) University of
Texas Southwestern Medical Center, Dallas, Texas
b) McGill University,
Canada and Immunotec Inc. Montreal, QC Canada
ABSTRACT – Purpose: To examine
the tolerability of non-denatured whey protein isolate (NWPI) in children with
autism. Many children with autism are low in glutathione and have higher levels
of oxidative stress. NWPI can raise glutathione levels and reduce oxidative
stress. However, anecdotal reports suggest that NWPI may be problematic in
children with autism because it contains cysteine and other sulfurated amino
acids.
Methods: A 6-week open-label trial was conducted,
supplementing 10 children with autism or autism spectrum disorder (ASD), 3-15
years of age, with NWPI (Immunocal®). To measure possible side effects,
procedures that examined the frequency, intensity, and types of side effects,
as well as behavioral measures, were completed at baseline, and at days 3, 14,
30 and 45.
Results: Seven of the
ten children took the supplement over the six-week trial and tolerated
it well. Two children discontinued after two weeks due to possible side
effects: one due to gastrointestinal disturbance and one due to being less
responsive to parents. Another child discontinued due to difficulty of
administering the product.
Conclusion: This study suggests that NWPI can
be used as a supplement for this small population of children with autism
without high rates of side effects, which means that further studies to
determine its safety and efficacy in larger populations might yield the same
promising result. Larger studies are planned to determine its efficacy in
raising glutathione levels.
PEDIATR BLOOD CANCER, 50:447-450 (2008)
34-CHILDREN’S
ONCOLOGY GROUP (COG) NUTRITION COMMITTEE
Paul C. Rogers,
MB ChB, MBA, 1* Steven J. Melnick, MD, PhD, 2, Elena J.
Ladas, MS, 3 Jacqueline Hamilton, MD,4 Jacques
Baillargeon, PhD,5 and Nancy Sacks, MS 6
1British Columbia Children’s Hospital,
Vancouver, British Columbia, Canada,
2Miami
Children’s Hospital, Miami, Florida,
3Columbia
University, Children’s Hospital of New York, NY,
4Children’s Hospital of Eastern Ontario,
Ottawa, Ontario, Canada, 5University of Texas Health Science Center,
San Antonio, Texas, 6The Children’s Hospital of Philadelphia,
Philadelphia, Pennsylvania.
Children’s Oncology Group (COG)
Nutrition Committee was established to further the knowledge of nutrition in
children with cancer by education and conduct of clinical trials. A survey of
COG institutions revealed lack of conformity in evaluation and categorization of
nutritional status, and criteria for nutritional intervention. The Committee
subsequently established specific categories of malnutrition (Underweight and
Overweight) based on ideal body weight or body mass index. An algorithm was
developed as a guideline for nutritional intervention as well as references and
resources for determining estimated needs. The Committee embarked on concepts
for clinical trials of nutritional interventions. The first pilot study,
evaluating the feasibility of using an immunoneutraceutical precursor for
glutathione production, has been completed. The study showed weight gain and
improvement in glutathione status. A pilot trial of proactive enteral feeding
for patients at high risk of malnutrition has commenced. The Committee believes
that nutrition is relevant to all aspects of cancer control. The paucity of
nutritional investigation in children with cancer needs to be rectified. Key
words: cancer, children; nutrition.
JOURNAL OF GASTROENTEROLOGY & HEPATOLOGY 24:1045-1050
(2009)
35-OPEN-LABELED PILOT STUDY OF CYSTEINE-RICH WHEY PROTEIN
ISOLATE
SUPPLEMENTATION
FOR NONALCOHOLIC STEATOHEPATITIS PATIENTS
Taned
Chitapanarux* Prasong Tienboon†, Suwalee Pojchamarnwiputh ‡ and Donrawee Leelarungrayub§
*Division
of Gastrohepatology, Department of Medicine, † Division of Nutrition, Department of
Pediatrics, ‡ Division of Diagnostic Radiology,
Department of Radiology, Faculty of Medicine, Chiang Mai University, and §
Department of Physical Therapy, Faculty of Associated Medical Sciences, Chiang
Mai University, Thailand.
Background and Aims: Glutathione (GSH) depletion
contributes to liver injury and development of steatohepatitis. Undenatured
cysteine-rich whey protein isolate has been clinically proven to raise GSH in
several patient groups. The aim of this study was to evaluate the effect of
oral supplementation with whey protein on patients with nonalcoholic
steatohepatitis (NASH).
Methods: In an
open-labeled clinical trial, 38 patients (18 male, 20 female; mean age
48 ± 14 years) with NASH confirmed by computed tomography measurements and
liver biochemistries were given with a daily dose of 20g whey protein isolate
for 12 weeks.
Results: A significant reduction in alanine aminotransferase
(ALT) (64 ± 72 vs 46 ± 36, P=0.016) and aspartate
aminotransferase (AST) (45 ± 49 vs 33 ± 18, P=0.047) were
observed. Plasma glutathione and total antioxidant capacity increased
significantly at the end of study (53 ± 11 vs 68 ± 11, P< 0.05 and
1.26 ± 0.10 vs 2.03 ± 0.10, P< 0.05). Liver attenuation index
improved from -13.4 ± 11.1 to -9.7 ± 13.1 (P = 0.048). Hepatic
macrovesicular steatosis decreased significantly after 12 weeks of
supplementation (33.82 ± 12.82 vs 30.66 ± 15.96, P=0.046). Whey
protein isolate was well tolerated. No serious adverse events were observed.
Conclusions: The
results indicate that oral supplementation of cysteine-rich whey protein
isolate leads to improvements in liver biochemistries, increased plasma GSH,
total antioxidant capacity and reduced hepatic macrovesicular steatosis in NASH
patients. The results support the role of oxidative stress in the pathogenesis
of this disease.
PRESENTED AT THE
INTERNATIONAL CONFERENCE ON AIDS; INT. CONF. AIDS AUG. 7-12, 1994 (Abstract no.
421A).
36-ANTI-HIV
AND ANTI-APOPTOTIC ACTIVITY OF THE WHEY PROTEIN CONCENTRATE: IMMUNOCAL.
Baruchel
S, Olivier R, Wainberg M.
Montreal
Children’s Hospital, Montreal, Quebec, Canada
OBJECTIVES: The in vivo glutathione (GSH)
promoting activity of undenatured Whey protein concentrate (WPC) has already
been demonstrated. Here we demonstrate the anti HIV and anti Apoptotic activity
of a WPC product termed IMMUNOCAL and its relation with GSH synthesis.
METHODS: IMMUNOCAL is
produced in linear fashion in order to maintain proteins in a non
denatured form and to preserve their glutamyl cysteine residues. We tested the
in vitro anti-HIV activity on cord blood mononuclear cells and MT 4 cells by
studying each of reverse transcriptase (RT) activity, p24 antigen production,
and syncytium formation. GSH was measured by spectrophotometric recycling
assay. Apoptosis was evaluated by flow cytometry on PBMC from HIV infected
individuals (cells were stained with acridine orange and ethidium bromide) (n =
6).
RESULTS: An anti HIV activity was found
at WPC concentrations between 100 micrograms/ml and 500 micrograms/ml.
Inhibition of syncytium formation occurred with a IC50 of 150 micrograms/ml.
PBMCs cultured with these WPC concentrations (N = 3) had a statistically
significant increase in GSH synthesis when compared to untreated cells, 9.6 +/-
1.5 vs 5.4 +/- nmoles/10(7) cells, p = 0.01. HIV infected PBMCs cultured in the
presence of 100 micrograms/ml of WPC were less prone to die of apoptosis than
untreated cells, 15% +/- 2.6 vs 37% +/- 2.4 p <0.001.
CONCLUSION: IMMUNOCAL
(WPC) possesses antiviral and anti-apoptotic activities which may be
related to its glutathione promoting activity. A clinical trial is currently
going on with children with AIDS and wasting syndrome.
TEMAS RELACIONADOS:
IMMUNOCAL DE IMMUNOTEC EN HERMOSILLO SONORA MEXICO
TELEFONO 6622821361 ORLANDO CARDENAS IMMUNOCAL DE IMMUNOTEC
LA CURA NATURAL DE LAS ENFERMEDADES UTILIZANDO NUTRACEUTICOS PARA FORTALECER EL SISTEMA INMUNOLOGICO SIN NINGUN EFECTO SECUNDARIO NEGATIVO IMMUNOCAL DE IMMUNOTEC
LA MEDICINA NATURAL AL ALCANCE DE TODOS IMMUNOCAL DE IMMUNOTEC
MEDICINA ALTERNATIVA IMMUNOCAL DE IMMUNOTEC
MEDICINA NATURAL IMMUNOCAL DE IMMUNOTEC
MEDICINA NUTRACEUTICA IMMUNOCAL DE IMMUNOTEC
MEDICINA ENERGETICA IMMUNOCAL DE IMMUNOTEC
MEDICINA HERBOLARIA IMMUNOCAL DE IMMUNOTEC
BLENDED MEDICINE IMMUNOCAL DE IMMUNOTEC
DOCTOR MD PHD MEDICO IMMUNOCAL DE IMMUNOTEC
REMEDIOS CON IMMUNOCAL DE IMMUNOTEC
EMPRESA CANADIENSE GUSTAVO BOUNOUS CANADA FDA PDR CPS MEDICARE
CARDIOLOGO IMMUNOCAL DE IMMUNOTEC
ONCOLOGO IMMUNOCAL DE IMMUNOTEC
NUTRIOLOGO IMMUNOCAL DE IMMUNOTEC
PEDIATRA IMMUNOCAL DE IMMUNOTEC
Especialidades:
Alergia e inmunología clínica
Alergia e inmunología clínica pediátrica
Anatomía patológica
Anestesiología
Anestesiología pediátrica
Angiología y cirugía vascular
Audiología
otoneurología y foniatría
Biología de la reproducción humana
Cardiología
Cardiología pediátrica
Cirugía cardiotorácica
Cirugía cardiotorácica pediátrica
Cirugía general
Cirugía oncológica
Cirugía pediátrica
Cirugía plástica y reconstructiva
Coloproctología
Dermatología
Dermatología pediátrica
Dermatopatología
Endocrinología
Endocrinología pediátrica
Epidemiología
Gastroenterología
Gastroenterología y nutrición pediátrica
Genética médica
Geriatría
Ginecología oncológica
Ginecología y obstetricia
Hematología
Hematología pediátrica
Imagenología diagnóstica y terapéutica
Infectología
Medicina de la actividad física y deportiva
Medicina de rehabilitación
Medicina de urgencias
Medicina del enfermo en estado crítico
Medicina del enfermo pediátrico en estado crítico
Medicina del trabajo y ambiental
Medicina familiar
Medicina interna
Medicina legal
Medicina maternofetal
Medicina nuclear
Nefrología
Nefrología pediátrica
Neonatología
Neumología
Neumología pediátrica
Neuroanestesiología
Neurocirugía
Neurocirugía pediátrica
Neurofisiología clínica
Neurología
Neurología pediátrica
Neurootología
Neuropatología
Neurorradiología
Nutriología clínica
Oftalmología
Oftalmología neurológica
Oncología médica
Oncología pediátrica
Ortopedia
Otorrinolaringología pediátrica
Otorrinolaringología y cirugía de cabeza y cuello
Patología clínica
Patología pediátrica
Pediatría
Psiquiatría
Psiquiatría infantil y de la adolescencia
Radiooncología
Reumatología
Reumatología pediátrica
Terapia endovascular neurológica
Urgencias pediátricas
Urología
Urología ginecológica.
grupos de edad (pediatría, geriatría)
aparatos o sistemas del cuerpo humano (neumología, cirugía vascular)
órganos (oftalmología, otorrinolaringología)
técnicas diagnósticas (radiología, microbiología)
técnicas terapéuticas y rehabilitadoras (farmacología, cirugía, ortopedia y traumatología, rehabilitación, hidrología)
enfermedades concretas (infectología, alergología, psiquiatría)
actividades humanas (medicina del trabajo, medicina del deporte, medicina legal, medicina preventiva)
La especialidad que abarca todos los anteriores apartados desde un visión integral del paciente es la medicina familiar y comunitaria.
[editar]Según su agrupación tradicional
Tradicionalmente se dividen en clínicas, quirúrgicas, y de laboratorio. Aunque con los continuos avances de la medicina, esos límites no son muy precisos.
[editar]Especialidades clínicas
Las especialidades médicas se corresponden con la figura tradicional de "médico": asisten personalmente al paciente con actividades preventivas, diagnósticas y terápéuticas, generalmente sin utilizar técnicas quirúrgicas.
Alergología
Anestesiología y Reanimación
Aparato Digestivo o Gastroenterología
Cardiología
Endocrinología y Nutrición
Geriatría
Hematología y Hemoterapia
Hidrología Médica
Infectología
Medicina del Deporte
Medicina del Trabajo
Medicina Familiar y Comunitaria
Medicina Intensiva
Medicina Interna
Medicina Legal y Forense
Medicina Preventiva y Salud Pública
Nefrología
Neumología
Neurología
Oncología Médica
Oncología Radioterápica
Pediatría
Psiquiatría
Rehabilitación
Reumatología
[editar]Especialidades quirúrgicas
Las especialidades quirúrgicas se corresponden con la figura de cirujano, y utilizan medios invasivos para tratar, modificar o extirpar físicamente la estructura patológica. Se dividen por sistemas.
Cirugía Cardiovascular
Cirugía General y del Aparato Digestivo
Cirugía Oral y Maxilofacial
Cirugía Ortopédica y Traumatología
Cirugía Pediátrica
Cirugía Plástica, Estética y Reparadora
Cirugía Torácica
Neurocirugía
[editar]Especialidades médico-quirúrgicas
Son las que habitualmente usan tanto técnicas invasivas (quirúrgicas) como no invasivas (farmacológicas, etc).
Angiología y Cirugía Vascular
Dermatología Médico-Quirúrgica y Venereología
Estomatología
Ginecología y Obstetricia o Tocología
Oftalmología
Otorrinolaringología
Urología
[editar]Especialidades de laboratorio
De apoyo a los demás médicos, realizan diagnósticos y sugieren tratamientos a los clínicos, por lo que en ellas la relación con el paciente es reducida.
Análisis Clínicos
Anatomía Patológica
Bioquímica Clínica
Farmacología Clínica
Inmunología
Medicina Nuclear
Microbiología y Parasitología
Neurofisiología Clínica
Radiodiagnóstico o Radiología
Alergologo
inmunologo
alergologo
patologo
anestesiologo
pediatra
angiologo
audiologo
otoneurologo
foniatrologo
biologo
quimico
Cardiologo
cirujano
oncologo
cirujano plastico
Coloproctologo
Dermatologo
Dermatopatologo
Endocrinologo
Epidemiologo
Gastroenterologo
nutriologo
Gastroenterologo
Ginecologo
Ginecologo
obstetra
gineco obstetra
ginecobstetra
Hematologo
Imagenologo
diagnóstico
terapéuta
Infectologo
Nefrologo
Neonatologo
Neumologo
Neuroanestesiologo
Neurofisiologo
Neurologo
Neurootologo
Neuropatologo
Neurorradiologo
Nutriologo clinico
Oftalmologo
Oftalmologo neurológo
osteopata
Otorrinolaringologo
Patologo
Psiquiatra
Radiooncologo
Reumatologo
Urologo
