I M Abstract Summary Of Med Pub

SUMMARY OF MEDICAL PUBLICATIONS ON
IMMUNOCAL/HMS 90
MEDICAL HYPOTHESES (1999) 53(4): 347-349 - ©1999 HARCOURT PUBLISHERS LTD. - ARTICLE NO. MEHY. 1998.0780

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 Because GSH is also essential to aerobic muscular
typically associated or follows a recognized or contraction, an undesirable competition for GSH
presumed infection. Abnormalities of both precursors between the immune and muscular
humoral and cellular immunity have been systems may develop. It is conceivable that the
demonstrated in a substantial proportion of patients priority of the immune system for the survival of
with CFS. The most consistent findings are of the host has drawn to this vital area the ever-
impaired lymphocyte responses to mitogen. As an diminishing GSH precursors, thus depriving the
antioxidant, glutathione (GSH) is essential for skeletal muscle of adequate GSH precursors to
allowing the lymphocyte to express its full potential sustain a normal aerobic metabolism resulting in
without being hampered by oxiradical fatigue and eventually myalgia. © 1999 Harcourt
accumulation. Hence, protracted challenge of the Publishers Ltd.
immunocytes may lead to cellular GSH depletion.

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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
1
Department of Surgery, Dalhousie University, Halifax, Nova Scotia:
2
Department of Surgery, McGill University, Montreal Quebec
3
Department of Pediatrics and Oncology, McGill University, Montreal, Quebec:
4
Department of Immunology and Microbiology, Dalhousie University, Halifax, Nova Scotia, Canada

ABSTRACT. Glutathione (GSH) concentration is months. In six patients the blood lymphocyte GSH
high in most tumor cells and this may be an levels were substantially above normal at the
important factor in resistance to chemotherapy. outset, reflecting high tumor GSH levels. Two
Previous in-vitro and animal experiments have patients (#1, #3) exhibited signs of tumor
shown a differential response of tumor versus regression, normalization of haemoglobin and
normal cells to various cysteine delivery systems. peripheral lymphocyte counts and a sustained drop
More specifically, an in-vitro assay showed that at of lymphocyte GSH levels towards normal. Two
concentrations that induce GSH synthesis in normal patients (#2, #7) showed stabilization of the tumor,
human cells, a specially prepared whey protein increased haemoglobin levels. In three patients
concentrate, Immunocal™, caused GSH depletion (#4, #5, #6) the disease progressed with a trend
and inhibition of proliferation in human breast toward higher lymphocyte GSH levels. These
cancer cells. On the basis of this information five results indicate that whey protein concentrate might
patients with metastatic carcinoma of the breast, deplete tumor cells of GSH and render than more
one of the pancreas and one of the liver were fed 30 vulnerable to chemotherapy.
grams of this whey protein concentrate daily for six

Clin Invest Med, 16: 204-209, 1993

C:DOCUMENTS AND SETTINGSAVIS BETANCOURTMY DOCUMENTSIM ABSTRACT SUMMARY OF MED PUB.DOC
1

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 replenishment per se was not likely the cause of
experiments, a pilot study was undertaken to increased body weight. The glutathione content of
evaluate the effect of undenatured, biologically the blood mononuclear cells was, as expected,
active, dietary whey protein in 3 HIV-seropositive below normal values in all patients at the beginning
individuals over a period of 3 months. Whey of the study. Over the 3-month period, GSH levels
protein concentrate was prepared so that the most increased and in one case rose by 70% to reach
thermosensitive proteins, such as serum albumin normal value. The increase in body weight
which contains 6 glutamylcysteine groups, would observed in these patients did not correlate with
be in undenatured form. Whey protein powder increase in energy or protein intake.
dissolved in a drink of the patient’s choice was
drunk cold in quantities that were increased In conclusion, these preliminary data indicate that,
progressively from 8.4 to 39.2 g per day. Patients in patients who maintain an adequate total caloric
took whey proteins without adverse side effects. In intake, the addition of “bioactive” whey protein
the 3 patients whose body weight had been stable in concentrate as a significant portion of total protein
the preceding 2 months, weight gain increased intake increases body weight and shows elevation
progressively between 2 and 7 kg, with 2 of the of glutathione (GSH) content of mononuclear cells
patients reaching ideal body weight. Serum toward normal levels. This pilot study will serve as
proteins, including albumin, remained unchanged a basis for a much larger clinical trial.
and within normal range, indicating that protein

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CLIN INVEST MED, 14: 296-309, 1991

4- THE BIOLOGICAL ACTIVITY OF UNDENATURED DIETARY WHEY PROTEINS:
ROLE OF GLUTATHIONE.

G. Bounous, P. Gold

Department of Surgery, Montreal General Hospital, Research Institute, Quebec

ABSTRACT – This study compared the effects of greater relative concentration of the thermolabile
different sources of whey protein concentrate (20 cystine rich proteins. In addition, the mice fed this
g/100 g diet) and of casein on the spleen, liver, and type of whey protein concentrate exhibit higher
heart glutathione content of C3H/HeJ mice, and on levels of tissue glutathione. The presence in the
the immune response of their spleen cells to sheep serum albumin fraction of glutamylcysteine groups
red blood cells. Body weight curves were similar (rare in food protein) and the specific
in all dietary groups. Our data indicate that the intramolecular bond as related to the undenatured
humoral immune response is highest in mice fed a conformation of the molecule are considered to be
dietary whey protein concentrate exhibiting the key factors in the glutathione-promoting activity of
highest solubility (undenatured conformation) and a the protein mixture.

CANCER LETTERS, 57: 91-94, 1991

2

5- WHEY PROTEINS IN CANCER PREVENTION

G. Bounous*, G. Batist** and P. Gold***

*Professor of Surgery, McGill University, and Career Investigator of the Medical Research Council of Canada,
**Director, Experimental Therapeutics, Department of Oncology, McGill University, ***Chairman, Department of
Medicine, McGill University, and Physician-in-Chief, The Montreal General Hospital.

ABSTRACT – Epidemiological and experimental diets result in increased glutathione (GSH)
studies suggest that dietary milk products may exert concentration in a number of tissues, and that some
an inhibitory effect on the development of several of the beneficial effects of whey protein intake are
types of tumors. Some recent experiments in abrogated by inhibition of GSH synthesis. Whey
rodents indicate that the antitumor activity of the protein is particularly rich in substrates for GSH
dairy products is in the protein fraction and more synthesis. We suggest that whey protein may be
specifically in the whey protein component of milk. exerting its effect on carcinogenesis by enhancing
We and others have demonstrated that whey protein GSH concentration.

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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 continuously fed the whey protein diet were found
influence of two formula diets containing 20 g/100 to be alive, whereas 33% of those on the casein or
g diet of either whey protein concentrate or casein, Purina diet had died. Animals fed Purina diet for
or Purina mouse chow on 1,2dimethylhydrazine 20 weeks and then switched to either milk protein
(DMH)-induced colon carcinoma in A/J mice. diet for a further 8 weeks exhibited a decrease in
Four weeks after the 24th DMH treatment the tumour burden as compared to those animals fed
incidence of tumour and tumour area in the whey the Purina diet continuously. Body weights were
protein-fed mice was substantially less in similar in all dietary groups. In conclusion, a whey
comparison to either the casein or Purina groups. protein diet appears to significantly influence the
The Purina group exhibited the greatest tumour development of chemically induced colon tumours
burden. At the end of the experiment all animals 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

3

ABSTRACT – This study compared the effects of a chow over the 6.3 month observation period
whey-rich diet (20 g / 100 g diet), with that of extending from the age of 21 months
Purina mouse chow or casein-rich diet (20 g / 100 g (corresponding to a human age of 55 years) to 26-
diet), on the liver and heart glutathione content and 27 months of age (corresponding to a human age of
on the survival of old male C57BL / 6 NIA mice. 80 years), during which time 55% mortality was
The study was performed during a limited observed. The corresponding mean survival time
observation period of 6.3 months. In mice fed the of mice fed the defined casein diet is almost
whey protein-rich diet between 17 months and 20 identical to that of Purina-fed controls. Body
months of age, the heart tissue and liver tissue weight curves were similar in all three dietary
glutathione content were enhanced above the groups. Hence, a whey protein diet appears to
corresponding values of the casein diet-fed and enhance the liver and heart glutathione
Purina-fed mice. Mice fed the whey protein diet at concentration in aging mice and to increase
the onset of senescence, exhibited increased longevity over a 6.3 month observation period.
longevity as compared to mice fed Purina mouse

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CLIN INVEST MED, 12: 154-61, 1989

8- IMMUNOENHANCING PROPERTY OF DIETARY WHEY PROTEIN IN MICE:
ROLE OF GLUTATHIONE

G. Bounous, G. Batist, P. Gold

Montreal General Hospital, Quebec

ABSTRACT – The spleen cells immune response more sustained production of splenic glutathione
to sheep red blood cells of C3H/HeJ mice fed a 20 during the antigen driven clonal expansion of the
g whey protein/100 g diet is substantially higher lymphocyte in whey protein fed mice in
than that of mice fed an equivalent casein diet of comparison to mice fed the equivalent casein or the
similar nutritional efficiency. The present study cysteine-enriched casein diet. Hence the efficiency
indicates that the observed immunoenhancing of dietary cysteine in inducing supernormal
effect of the whey protein mixture is dependent on glutathione levels is greater when it is delivered in
the overall amino acid pattern resulting from the the whey protein than as free cysteine.
contribution of all its protein components. Whey Administration of S-(n-butyl) homocysteine
protein contains substantially more cysteine than sulfoximine, which reduces splenic glutathione
casein. Dietary cysteine is considered to be a rate level by half, produces a 4-5 fold drop in the
limiting substrate for the synthesis of glutathione humoral immune response of whey protein diet-fed
which is necessary for lymphocyte proliferation. mice. This is further evidence of the important role
Our studies show that enhancement of host humoral of glutathione in the immunoenhancing effect of
immune response is associated with greater and 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
1
The Montreal General Hospital Research Institute, 2[)epartments of Surgery, 3Physiology, and
4
Medicine, McGill University, Montreal, Quebec
(ORIGINAL MANUSCRIPT SUBMITTED OCTOBER 22, 1987: ACCEPTED IN REVISED FORM JANUARY 25, 1988)

ABSTRACT - The plaque-forming cell response to formula diets of similar nutritional efficiency
sheep red blood cells was found to be enhanced in containing 20 g / 100 g diet of either casein, soy,
mice fed a formula diet containing 20 g lactalbumin wheat or corn protein, egg albumin, beef or fish
/100 g diet in comparison to mice fed equivalent protein, Spirulina maxima, or Scenedesmus protein,

4

or Purina mouse chow. This effect was manifest response in comparison to that of mice fed diets
after 2 weeks and persisted for at least 8 weeks of containing 20% soy protein or casein.
dietary treatment. Mixing lactalbumin with either
casein or soy protein in a 20 g protein / 100 g diet key words: dietary whey protein, humoral immune
formula significantly enhanced the immune response.

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CLIN INV MED, 11: 213-217, 1988

10- DIETARY WHEY PROTEIN INHIBITS THE DEVELOPMENT OF
DIMETHYLHYDRAZINE-INDUCED MALIGNANCY

G. Bounous*, R. Papenburg*, P.A.L Kongshavn**, P. Gold†, and D. Fleiszer*

Departments of Surgery*, Physiology**, and Medicine†, Montreal General Hospital and McGill University

ABSTRACT – This study investigates the influence treatment the incidence of tumors in the whey
of two formula diets containing 20 g/100 g diet of protein-fed mice was substantially lower than that
either whey protein concentrate or casein or Purina in mice fed either the casein or Purina diet.
mouse chow, on the humoral immune Similarly, the tumor area was less in the whey
responsiveness and dimethylhydrazine induced protein group in comparison to either the casein or
colon carcinogenesis in A/J mice. After 20 weeks Purina groups, with some difference between
of dimethylhydrazine treatment, the number of casein and Purina groups. Body weight curves
plaque forming cells per spleen, following were similar in all dietary groups.
intravenous inoculation with 5 x 106 sheep red
blood cells, was nearly three times greater in the In conclusion, a whey protein diet appears to
whey protein-fed group than in the casein-fed mice significantly inhibit the incidence and growth of
although both values were substantially below chemically induced colon tumors in mice.
normal. After 24 weeks of dimethylhydrazine

J. NUTR. 115: 1409-1417, 1985

11- 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 or non purified diet. A similar pattern of dietary
lactalbumin (L) or casein (C) diets or a nonpurified protein effect in (CBA/N x DBA/2J) F1 mice
(NP) diet on the immune responsiveness of carrying the xid defect was observed following
C57B1/6J, C3H/HeJ and BALB/cJ mice has been challenge with sheep red blood cells (SRBC). An
investigated by measuring the response to the T even greater enhancing effect of dietary L was
cell-independent antigen, TNP-Ficoll. To noted in normal (DBA/2J x CBA/N) F1 mice after
investigate the possible influence of dietary protein immunization with SRBC, but in contrast, the
type on the supply of B lymphocytes, bone marrow normal large-scale production of B lymphocytes in
lymphocyte production has been examined by a mouse bone marrow was independent of the type of
radioautographic assay of small lymphocyte dietary protein. Dietary protein type did not affect
renewal and an immuno-fluorescent stathmokinetic blood level of minerals and trace metals. The free
assay of pre-B cells and their proliferation. The plasma amino acid profile essentially conformed to
humoral response of all mice fed the L diet was the amino acid composition of the ingested protein,
found to be higher than that of mice fed the C diet suggesting that the changes in plasma amino acid

5

profile might be a crucial factor in diet-dependent functional responsiveness of the B lymphocytes
enhancement or depression of the B-cell response. themselves or in the processes leading to their
The findings indicate that the observed effects of activation and differentiation in the peripheral
altered dietary protein type on humoral immune lymphoid tissues.
responsiveness are not exerted centrally on the rate
of primary B-lymphocyte production in the bone INDEXING KEY WORDS: DIET – PROTEIN – IMMUNITY
marrow, but may reflect changes either in the – B-CELL RESPONSE - MICE

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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 differ among mice fed the various diets. Similarly,
lactalbumin (L), casein (C), soy (S) and wheat (W) the type of diet did not appear to influence host
protein on the immune responsiveness of C3H/HeN resistance to Salmonella typhymurium. It is
mice has been investigated by measuring the postulated that the type of protein in the diet
humoral immune response to the T cell- influences directly the intrinsic capacity of the B
independent antigen, TNP-Ficoll. The humoral lymphocytes to respond to an immunogenic
immune response of mice fed the L diet was found stimulus.
to be higher than that of mice fed the C, S and W
diets. On the other hand, delayed-type Indexing Key Words: diet * protein * immunity *
hypersensitivity, and splenic cell mitogen responses mice
to phytohemagglutinin and concanavalin A did not
J. NUTR. 113: 1415-1421, 1983

13- INFLUENCE OF DIETARY PROTEIN TYPE ON THE IMMUNE SYSTEM OF MICE

G. Bounous, L. Létourneau and P.A.L. Kongshavn†

Centre hospitalier universitaire, Sherbrooke, Quebec, Canada; J1H 5N4 and †Montreal General Hospital Research

ABSTRACT – The effect of graded amounts of substantially lower than that of mice fed stock diet,
dietary lactalbumin (L), casein (C), soy (S), wheat whereas that of mice fed L diet was higher. The
(W) protein and Purina rodent chow (stock diet) on above-described immune effect of all tested
the immune responsiveness of C3H/HeN mice has proteins was obtained at 20 g/100 g concentration
been investigated by measuring the specific with no further increments with 30- and 40 g/100 g
humoral immune response to sheep red blood cells protein in the diet. Mitogen responsiveness to PHA
(SRBC), and horse red blood cells (HRBC) as well and Con A in L diet-fed mice was only slightly
as the nonspecific splenic cell responsiveness to higher than that of C diet-fed mice. Little
phyto-hemagglutinin (PHA) and concanavalin A difference in immune responses was noted among
(Con A) after stimulation with Myco-bacterium mice fed C, S or W protein diets. The principal
bovis, strain BCG. The nutritional efficiency of factor responsible for the observed immune effect
these diets was normal and similar. The immune does not appear to be the availability or
response of mice fed the L diets, was found to be concentration of single essential amino acids but
almost five times higher than that of mice fed the rather the composite effect of the specific amino
corresponding C diets. The humoral immune acid distribution in the protein.
response of mice fed C, S, and W diets was

6

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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 whole content analyzed by ELISA to determine S-
splenic immune response to sheep red blood cells IgA secretion. Body weight curves were similar in
(SBRC) in mice. This study was designed to all dietary groups; higher biliary levels of S-IgA
investigate the influence of the type of dietary appeared in the whey protein fed mice than in the
protein on the biliary secretory IgA. A/J mice were casein (p less than 0.025) or purine (p less than
fed defined formula diets containing either 20% 0.025) fed mice. Dietary protein type may have a
whey protein, or 20% casein. Another group was direct influence on the immune response in the
fed Purina mouse chow. After 3 weeks of dietary gastrointestinal tract, without affecting body
treatment the body weight of each mouse was weight.
recorded and the gall-bladder was removed and its

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
1
McGill 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 agents promoting GSH synthesis, are discussed.
of HIV replication in vitro, has a potential role as a The review also includes the early results of
cofactor of HIV disease progression. Arguments nutritional interventions based on a diet enriched
supporting the role of oxidative stress as a cofactor with IMMUNOCAL™, a whey protein concentrate
in HIV activation are summarized in this review. prepared in a proprietary manner.
The role of intracellular antioxidants such as
glutathione (GSH), and drugs and nutriceutical

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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†
o
Centre Hospitalier Universitaire, Sherbrooke, Quebec, Canada, J1H 5N4 and †Montreal General Hospital Research

ABSTRACT The effect of graded amounts of measuring both the specific humoral immune
dietary laetalbumin (L) and casein (C) hydrolyzates response to sheep red blood cells (SRBC) and the
on the immune responsiveness of C3H/HeN and nonspecific splenic cell responsiveness to
DBA/2 strain mice has been investigated by phytohemagglutinin, concanavalin A and

7

Escherichia coli lipopolysaccharide after diet was seen, but there was no change in the
stimulation with Mycobacteriurn bovis, strain BCG. humoral immune response. The enhancement of
The nutritional efficiency of these diets was similar immune responsiveness observed in mice fed the
at both 12 and 28% amino acid levels. The immune 28% L diet was moderately reduced by the addition
responses of mice fed the L diets were found to be of phenylalanine to the diet, indicating that the
significantly greater than those of mice fed the lower level of this amino acid in the L protein may
corresponding C diets, especially at the 28% level. be of some significance. These dietary effects on
Furthermore in the mice fed L diet, increasing the immune responsiveness were remarkably similar in
concentration of amino acid in the diet from 12 to both mouse strains tested.
28% greatly enhanced immune responsiveness by
both parameters measured. In the C-fed mice, a INDEXING KEY WORDS: diet - protein –
comparable enhancement of mitogen immunity - mice
responsiveness with increasing amino acid level of

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 in the diet above the minimum requirement (12%
the effect of four weeks of treatment with a diet LAH) and thus produce augmented humoral
containing lactalbumin hydrolysate (LAH: Nestlé, immune responsiveness and resistance to
Vevey, Switzerland) on the immune response of salmonellosis.
C3H/HeN mice. Our data indicate that it was
possible to increase the level of this type of protein Lactalbumin = Whey Protein Concentrate

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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 gm/day) or casein placebo. Muscular performance
muscular fatigue. Glutathione (GSH) is the major was assessed by whole leg isokinetic cycle testing,
intracellular antioxidant, whose biosynthesis is measuring Peak Power and 30-sec Work Capacity.
dependent upon cysteine availability. We Lymphocyte GSH was used as a marker of tissue
hypothesized that supplementation with a whey- GSH. There were no baseline differences (age, ht,
based cysteine donor (Immunocal (HMS90)) wt, % ideal wt, Peak Power, 30-sec Work
designed to augment intracellular GSH, would Capacity). Follow-up data on 18 subjects (9
enhance performance. Twenty healthy young Immunocal, 9 placebo) were analyzed. Both Peak
adults (10 m) were studied pre- and 3 months post- Power (mean±se: 13±3.5%, p<0.02) and 30-sec
supplementation with either Immunocal (20 Work Capacity (13±3.7%, p<0.03) increased

8

significantly in the Immunocal group, with no supplementation with a product designed to
change (2±9.0 and 1±9.3%) in the placebo group. augment antioxidant defenses resulted in improved
Lymphocyte GSH also increased significantly in volitional performance.
the Immunocal group (35.5±11.04%, p<0.02) with
no change in the placebo group (-0.9±9.6%). This Key words: oxidative stress, exercise
is the first study to demonstrate that prolonged

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 glutathione levels. Following one month of
occur in obstructive airways disease, as a result of supplementation with a whey-based oral
ongoing inflammation. Glutathione plays a major supplement, designed to provide glutathione
role in pulmonary antioxidant protection. As an precursors, whole blood glutathione levels and
alternative or complement to anti-inflammatory pulmonary function significantly and dramatically
therapy, augmenting antioxidant protection could increased. The potential for such supplementation
diminish the effects of inflammation. We describe in pulmonary inflammatory conditions deserves
a case of a patient with obstructive lung disease, further study.
responsive to corticosteroids, with low whole blood

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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 (follow-up period). The effects of Immunocal food
protein (Immunocal: cysteine content; 7.6-fold that on various clinical parameters were examined at 4-
of casein) isolated from fresh milk and purified week intervals for 18 weeks to evaluate the efficacy
without being heated was evaluated based on liver of Immunocal. As a result, serum ALT activity
function test, immunological parameters, plasma or decreased in 6 of 8 patients with chronic hepatitis B
lymphocyte GSH concentrations and hepatitis virus 12 weeks after the start of supplement with
markers in 25 patients with chronic hepatitis B or Immunocal food. Plasma GSH concentrations were
C. Immunocal (12 g as protein) food (mousse) was increased in 5 of the 8 patients. Serum .
given twice a day, in the morning and evening, for concentrations of lipid peroxides significantly
12 weeks (test period). Casein (12 g as protein) decreased 8 weeks after Immunocal food. Serum
food (mousse) was given for 2 weeks prior to the IL-2 levels began to increase 8 weeks and remained
start of -supplement with Immunocal food high even after supplement with Immunocal -food
(induction period) and for 4 weeks after the end had ended. Furthermore, NK activity was

9

significantly increased. However, an item that long-term supplement with Immunocal alone
correlating with reduced serum ALT activity could may be effective for patients with chronic hepatitis
not be clarified. In 17 patients with chronic B, and a further clinical study that long-term
hepatitis C, there wore no significant Immunocal- combination therapy with Immunocal and other
related changes in liver function test or agents including interferon may be effective for
immunological parameters. These findings suggest 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 proteins also exhibit anti-carcinogenesis and
system is foremost among the cellular protective anticancer activity. They do this via their effect on
mechanisms. Depletion of this small molecule is a increasing GSH concentration in relevant tissues,
common consequence of increased formation of and may have anti-tumor effect on low volume of
reactive oxygen species during increased cellular tumor via stimulation of immunity through the
activities. This phenomenon can occur in the GSH pathway. It is considered that oxygen radical
lymphocytes during the development of the generation is frequently a critical step in
immune response and in the muscular cells during carcinogenesis, hence the effect of GSH on free
strenuous exercise. It is not surprising that so much radicals as well as carcinogen detoxification, could
research has been done, and is still being done on be important in inhibiting carcinogenesis induced
this small tripeptide molecule. Whey protein by a number of different mechanisms. Case reports
concentrate has been shown to represent an are presented which strongly suggest an anti-tumor
effective and safe cysteine donor for GSH effect of a whey protein dietary supplement in some
replenishment during GSH depletion in immune urogenital cancers. This non toxic dietary
deficiency states. Cysteine is the crucial limiting intervention, which is not based on the principles of
amino acid for intracellular GSH synthesis. Animal current cancer chemotherapy, will hopefully attract
experiments showed that the concentrates of whey 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 compared to the cells grew in baicalein medium; in
of a whey protein isolate on the cytotoxicity of a contrast, for the cells grew in Immunocal™ group,
potential anti-cancer drug. baicalein, human there was no significant difference on survival rate.
hepatoma cell line HepG2 was assigned to grow in In the investigation of apoptosis. compared to the
different media for four days, followed by the cells in baicalein medium, cells in combined
investigation of cell growth and apoptosis. medium showed a higher phosphatidylserine
Excluding the control group with normal medium, exposure, lower rnitochondrial transmembrane
other three treatment media included whey protein potential and nearly 13 times more cells were
isolate (marketed as Immunocal™) medium, detected undergoing apoptosis. We also
baicalein medium, and combined medium demonstrated that Immunocal™ was able to reduce
containing both Irnmunocal™ and baicalein. MTT glutathione in HepG2 by 20% to 40% and regulated
assay indicated that cells grew in combined the elevation of glutathione, which was in response
medium had a significantly lower survival rate to baicalein. In conclusion, Immunocal™ seemed to

10

enhance the cytotoxicity of baicalein by inducing vitro, that Immunocal™ may function as an
more apoptosis, this increase in apoptotic cells may adjuvant in cancer treatments.
be in association with the depletion of GSH in
HepG2. This is the first study to demonstrate, in

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 oxidative stress and pathology of GSH metabolism
proteins isolated from cow’s milk in Immunocal™ are largely implicated. In a pilot study, this type of
depends on the preservation of those labile proteins whey protein concentrate was found to be well
which share with the predominant human milk tolerated in children with AIDS and wasting
proteins the same extremely rare glutathione syndrome and was found associated with an
(GSH)-promoting components. Cellular GSH improvement of the nutritional status of the patient.
depletion has been implicated in the pathogenesis Moreover, the GSH promoting activity on the
of a number of degenerative conditions and disease peripheral blood lymphocyte of this protein
states including Parkinson’s, Alzheimer’s, concentrate was validated in patients with initial
arteriosclerosis, cataracts, cystic fibrosis, low GSH levels. Extensive pharmaco-
malnutrition, aging, AIDS, and cancer. epidemiological study of GSH metabolism and
standardized methods of measurement of
This newly discovered nutriceutical modulation of intracellular GSH applicable in clinical trials are
GSH by the use of humanized native milk serum needed in order to better define the clinical
protein isolate of bovine origin in AIDS and cancer application of this new type of therapy.
may well find other applications in disease where

*****************************

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) for GSH replenishment during the immune
antioxidant system is the principal protective response. Animal experiments showed that the
mechanism of the cell and is a crucial factor in concentrates of whey protein also exhibit
the development of the immune response by the anticancer activity. They do this via the GSH
immune cells. Experimental data demonstrate pathway, the induction of p53 protein in
that a cysteine-rich whey protein concentrate transformed cells and inhibition of
represents an effective cysteine delivery system neoangiogenesis.

11

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 ± 261), HNE (912 ± 38) and hexanal (5385 ±
cause of organ failure worldwide, but its 927) were observed in the heart tissue of the
pathogenesis remains to be elucidated. group receiving iron with whey, in comparison
To examine in an experimental murine with the iron-only treatment group (MDA 9307 ±
model of iron-overload cardiomyopathy the 387, HNE 1416 ± 157, hexanal 14,874 ± 2955;
relation between milk whey protein and, first, the P<0.001). Significantly increased GPx (141 ±
production of reactive oxygen free radical 38 IU/L) and GSH (521 ± 136 IU/L) activity
species and, second, antioxidant reserve status. were observed in mice receiving iron with whey,
B6D2F1 mice were randomly assigned to in comparison with mice receiving iron only
four treatment groups (n=8 per treatment group): (GPx 100 ± 10 IU/L, GSH 446 ± 33 IU/L;
placebo control; iron only; whey only; and iron P<0.001).
with whey. Reactive oxygen free radical species Mice receiving iron treatments with whey
in the heart were quantified by the cytotoxic supplementation had significantly lower
aldehydes malondialdehyde (MDA), 4-hydroxy- concentrations of cytotoxic aldehydes and
nonenal (HNE) and hexanal, while antioxidant significantly higher cardiac levels of GPx and
reserve status was quantified by glutathione GSH activity than did iron-only treated mice.
(GSH) and glutathione peroxidase (GPx) activity Additional basic research is warranted to
in the heart tissue. examine the exact mechanisms by which milk
Significantly decreased concentrations whey protein protects the heart.
(pmol/100 mg wet weight tissue) of MDA (2468

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12

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