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IMMUNOCAL/HMS 90
1
MEDICAL HYPOTHESES (1999) 53(4): 347-349 - 1999 HARCOURT PUBLISHERS LTD. - ARTICLE NO. MEHY. 1998.0780
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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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
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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G. Bounous, P. Gold
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.
*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.
*********************************
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.
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 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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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.
ABSTRACT - The plaque-forming cell response to dietary treatment. Mixing lactalbumin with either
sheep red blood cells was found to be enhanced in casein or soy protein in a 20 g protein / 100 g diet
mice fed a formula diet containing 20 g lactalbumin formula significantly enhanced the immune
/100 g diet in comparison to mice fed equivalent response in comparison to that of mice fed diets
formula diets of similar nutritional efficiency containing 20% soy protein or casein.
containing 20 g / 100 g diet of either casein, soy,
wheat or corn protein, egg albumin, beef or fish key words: dietary whey protein, humoral immune
protein, Spirulina maxima, or Scenedesmus protein, response.
or Purina mouse chow. This effect was manifest
after 2 weeks and persisted for at least 8 weeks of
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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
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
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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
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 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
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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
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
********************************
ABSTRACT The effect of graded amounts of 28% greatly enhanced immune responsiveness by
dietary laetalbumin (L) and casein (C) hydrolyzates both parameters measured. In the C-fed mice, a
on the immune responsiveness of C3H/HeN and comparable enhancement of mitogen
DBA/2 strain mice has been investigated by responsiveness with increasing amino acid level of
measuring both the specific humoral immune diet was seen, but there was no change in the
response to sheep red blood cells (SRBC) and the humoral immune response. The enhancement of
nonspecific splenic cell responsiveness to immune responsiveness observed in mice fed the
phytohemagglutinin, concanavalin A and 28% L diet was moderately reduced by the addition
Escherichia coli lipopolysaccharide after of phenylalanine to the diet, indicating that the
stimulation with Mycobacteriurn bovis, strain BCG. lower level of this amino acid in the L protein may
The nutritional efficiency of these diets was similar be of some significance. These dietary effects on
at both 12 and 28% amino acid levels. The immune immune responsiveness were remarkably similar in
responses of mice fed the L diets were found to be both mouse strains tested.
significantly greater than those of mice fed the
corresponding C diets, especially at the 28% level. INDEXING KEY WORDS: diet - protein –
Furthermore in the mice fed L diet, increasing the immunity - mice
concentration of amino acid in the diet from 12 to
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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Bryce Lothian, MD*, Vijaylaxmi Grey, PhD*†, R. John Kimoff, MD‡, Larry Lands, MD, PhD*§
‡Division of Respiratory Medicine, McGill University Health Centre-Royal Victoria Hospita, Montreal, Quebec,
Canada
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PR514
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 Immunocal food. Plasma GSH concentrations were
protein (Immunocal: cysteine content; 7.6-fold that increased in 5 of the 8 patients. Serum .
of casein) isolated from fresh milk and purified concentrations of lipid peroxides significantly
without being heated was evaluated based on liver decreased 8 weeks after Immunocal food. Serum
function test, immunological parameters, plasma or IL-2 levels began to increase 8 weeks and remained
lymphocyte GSH concentrations and hepatitis virus high even after supplement with Immunocal -food
markers in 25 patients with chronic hepatitis B or had ended. Furthermore, NK activity was
C. Immunocal (12 g as protein) food (mousse) was significantly increased. However, an item
given twice a day, in the morning and evening, for correlating with reduced serum ALT activity could
12 weeks (test period). Casein (12 g as protein) not be clarified. In 17 patients with chronic
food (mousse) was given for 2 weeks prior to the hepatitis C, there wore no significant Immunocal-
start of -supplement with Immunocal food related changes in liver function test or
(induction period) and for 4 weeks after the end immunological parameters. These findings suggest
(follow-up period). The effects of Immunocal food that long-term supplement with Immunocal alone
on various clinical parameters were examined at 4- may be effective for patients with chronic hepatitis
week intervals for 18 weeks to evaluate the efficacy B, and a further clinical study that long-term
of Immunocal. As a result, serum ALT activity combination therapy with Immunocal and other
decreased in 6 of 8 patients with chronic hepatitis B agents including interferon may be effective for
12 weeks after the start of supplement with those with chronic hepatitis C should be performed.
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.
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ABSTRACT – To determine the enhancing effect cells in baicalein medium, cells in combined
of a whey protein isolate on the cytotoxicity of a medium showed a higher phosphatidylserine
potential anti-cancer drug. baicalein, human exposure, lower rnitochondrial transmembrane
hepatoma cell line HepG2 was assigned to grow in potential and nearly 13 times more cells were
different media for four days, followed by the detected undergoing apoptosis. We also
investigation of cell growth and apoptosis. demonstrated that Immunocal was able to reduce
Excluding the control group with normal medium, glutathione in HepG2 by 20% to 40% and regulated
other three treatment media included whey protein the elevation of glutathione, which was in response
isolate (marketed as Immunocal) medium, to baicalein. In conclusion, Immunocal seemed to
baicalein medium, and combined medium enhance the cytotoxicity of baicalein by inducing
containing both Irnmunocal and baicalein. MTT more apoptosis, this increase in apoptotic cells may
assay indicated that cells grew in combined be in association with the depletion of GSH in
medium had a significantly lower survival rate HepG2. This is the first study to demonstrate, in
compared to the cells grew in baicalein medium; in vitro, that Immunocal may function as an
contrast, for the cells grew in Immunocal group, adjuvant in cancer treatments.
there was no significant difference on survival rate.
In the investigation of apoptosis. compared to the
*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
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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.
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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G. Bounous, D. Beer
ABSTRACT – Studies in laboratory animals Association for Cancer Research indicates that
indicate inhibition of chemically-induced higher levels of total cysteine in plasma may
carcinoma by cystine-rich diets enhancing the predict a reduced risk for breast cancer. This
cysteine-GSH antioxidant system. The prospective investigation was conducted among
progression of carcinoma of the prostate is also 32,000 women in the Nurses Health study. The
inhibited by these diets, which were later found previously reported prostate cancer data appears
to raise the level of GSH in the prostate then not to be strictly gender-related as the
epithelium of man. New data presented at the antioxidant role of the cysteine – GSH system
July 13, 2003 meeting of the American may also apply to breast cancer prevention.
* ****************************
American College of Sports Medicine. Marywood University, Human Performance Laboratory, Scranton, PA
* ****************************
W. Dröge,
* ****************************
ABSTRACT – The mechanisms leading to the enhanced by oxidative stress in the absence of
increase in free-radical-derived oxidative stress insulin. This synopsis of seemingly unrelated
in “normal aging” remained obscure. Here we processes reveals a novel mechanism of
present our perspective on studies from different progressive oxidative stress in which decreasing
fields which reveal a previously unnoticed antioxidant concentrations and increasing basal
vicious cycle of oxidative stress. The plasma (postabsorptive) insulin receptor signaling
cysteine concentrations during starvation in the activity compromise not only the autophagic
night and early morning hours (the protein catabolism but also the activity of FOXO
postabsorptive state) decreases with age. This transcription factors, i.e. two functions which
decrease is associated with a decrease in tissue were found to have an impact on lifespan in
concentrations of the cysteine derivative and several animal models of aging. In addition, the
quantitatively important antioxidant glutathione. aging-related decrease in glutathione level is
The decrease in cysteine reflects changes in the likely to facilitate certain “secondary” disease-
autophagic protein catabolism which normally related mechanisms of oxidative stress. Studies
ensures free amino acid homeostasis during on cysteine supplementation show therapeutic
starvation. Autophagy is negatively regulated by promise.
the insulin receptor signaling cascade, which is
* ****************************
ABSTRACT – Oxidative stress plays a role in the estimated survival of > 3 months. Thirty-five lung
tumor-cytotoxic effect of cancer chemotherapy cancer patients remained on study at six weeks.
and radiotherapy and also in certain adverse Overall compliance was not different between
events. In view of these conflicting aspects, a treatment arms (42-44% or 13g/day). The patients
double-blind trial over 6 months has been treated with the cysteine-rich protein had a mean
performed to determine whether a cysteine-rich increase of 2.5% body weight while casein-treated
protein (IMN1207) may have a positive or patients lost 2.6% (P=0.049). Differences in
negative effect on the clinical outcome if secondary end points included an increase in
compared with casein, a widely used protein survival, hand grip force and quality of life.
supplement low in cysteine. Sixty-six patients Adverse events were mild or moderate. Further
with Stage IIIB-IV non-small cell lung cancer studies will have to show whether the positive
were randomly assigned to IMN1207 or casein. clinical effects can be confirmed and related to
Included were patients with a previous involuntary specific parameters of oxidative stress in the host.
weight loss of ≥3%, Karnofsky status ≥70, and an
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Janet K. Kern, PhD* University of Texas Southwestern Medical Center, and the Autism Treatment Center,
Dallas, Texas, Bruce D. Grannemann, MA; University of Texas Southwestern Medical Center, Dallas,
Texas; Jimmy Gutman, MD, FACEP, McGill University, Canada, and Immunotec Corporation, Montreal,
Quebec, Canada, Madhukar H. Trivedi, MD, University of Texas Southwestern Medical Center, Dallas,
Texas
* Correspondence:
Janet K. Kern, PhD
Autism Treatment Center
10503 Metric Drive
Dallas, Texas 75243
Phone: 972-644-2076 Fax: 972-644-5650
E-mail: jkern@atcoftexas.org
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.