Immunotec-Related Scientific Publications

 

Competition for glutathione precursors between the immune system and the skeletal muscle: pathogenesis of chronic fatigue syndrome.

Abstract

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.


Top of Page

https://www.ncbi.nlm.nih.gov/pubmed/10608272

The use of a whey protein concentrate in the treatment of patients with metastatic carcinoma: a phase I-II clinical study.

Abstract

Glutathione (GSH) concentration is high in most tumour cells and this may be an important factor in resistance to chemotherapy. Previous in-vitro and animal experiments have shown a differential response of tumour 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 tumour GSH levels. Two patients (#1, #3) exhibited signs of tumour regression, normalization of haemoglobin and peripheral lymphocyte counts and a sustained drop of lymphocyte GSH levels towards normal. Two patients (#2, #7) showed stabilisation of the tumour, 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 tumour cells of GSH and render them more vulnerable to chemotherapy.

Top of Page

https://www.ncbi.nlm.nih.gov/pubmed/8669840

Whey proteins as a food supplement in HIV-seropositive individuals.

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, glutathione levels increased in all 3 cases. In conclusion, these preliminary data indicate that, in patients who maintain an adequate total caloric intake, the addition of “bioactive” whey protein concentrate as a significant portion of total protein intake increases body weight and shows elevation of glutathione (GSH) content of mononuclear cells toward normal levels. This pilot study will serve as a basis for a much larger clinical trial.
Top of Page

https://www.ncbi.nlm.nih.gov/pubmed/8365048

The biological activity of undenatured dietary whey proteins: role of glutathione.

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 bovine serum albumin and immunoglobulins. 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.
Top of Page

https://www.ncbi.nlm.nih.gov/pubmed/1782728

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.
Top of Page

https://www.ncbi.nlm.nih.gov/pubmed/2025891

Dietary milk proteins inhibit the development of dimethylhydrazine-induced malignancy.

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 1,2-dimethylhydrazine (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.
Top of Page

https://www.ncbi.nlm.nih.gov/pubmed/2343238

The influence of dietary whey protein on tissue glutathione and the diseases of aging.

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/6NIA 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 significantly above the corresponding values of the casein diet-fed and Purina-fed mice. Mice fed the whey protein diet at the onset of senescence at 84 weeks, 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.
Top of Page

https://www.ncbi.nlm.nih.gov/pubmed/2692897

Immunoenhancing property of dietary whey protein in mice: role of glutathione.

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.
Top of Page

https://www.ncbi.nlm.nih.gov/pubmed/2743633

The immunoenhancing property of dietary whey protein concentrate.

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.
Top of Page

https://www.ncbi.nlm.nih.gov/pubmed/3168349

Dietary whey protein inhibits the development of dimethylhydrazine induced malignancy.

Abstract

This study investigates the influence of two formula diets containing 20 g/100 g diet of either whey protein concentrate or casein or Purina mouse chow, on the humoral immune responsiveness and dimethylhydrazine induced colon carcinogenesis in A/J mice. After 20 weeks of dimethylhydrazine treatment, the number of plaque forming cells per spleen, following intravenous inoculation with 5 X 10(6) sheep red blood cells, was nearly three times greater in the whey protein-fed group than in the casein-fed mice although both values were substantially below normal. After 24 weeks of dimethylhydrazine treatment the incidence of tumors in the whey protein-fed mice was substantially lower than that in mice fed either the casein or Purina diet. Similarly, the tumor area was less in the whey protein group in comparison to either the casein or Purina groups, with some difference between casein and Purina groups. Body weight curves were similar in all dietary groups. In conclusion, a whey protein diet appears to significantly inhibit the incidence and growth of chemically induced colon tumors in mice.
Top of Page

https://www.ncbi.nlm.nih.gov/pubmed/3402106

Mechanism of altered B-cell response induced by changes in dietary protein type in mice.

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 C57Bl/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 immunofluorescent 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 nonpurified 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.
Top of Page

https://www.ncbi.nlm.nih.gov/pubmed/3903076

Differential effect of dietary protein type on the B-cell and T-cell immune responses in mice.

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 typhimurium. 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.
Top of Page

https://www.ncbi.nlm.nih.gov/pubmed/3877153

Influence of dietary protein type on the immune system of mice.

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 phytohemagglutinin (PHA) and concanavalin A (Con A) after stimulation with Mycobacterium 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.
Top of Page

https://www.ncbi.nlm.nih.gov/pubmed/6864340

Changes in biliary secretory immunoglobulins A in mice fed whey proteins

Abstract

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.
Top of Page

https://www.ncbi.nlm.nih.gov/pubmed/2622564

Place for an Antioxidant Therapy in Human Immunodeficiency Virus (HIV) Infection

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.
Top of Page

View Article

Influence of dietary proteins on the immune system of mice.

Abstract

The effect of graded amounts of dietary lactalbumin (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 Mycobacterium 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.
Top of Page

https://www.ncbi.nlm.nih.gov/pubmed/7050321

Influence of dietary lactalbumin hydrolysate on the immune system of mice and resistance to salmonellosis.

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.

Lactalbumin = Whey Protein Concentrate

Top of Page

https://www.ncbi.nlm.nih.gov/pubmed/7024433

Effect of supplementation with a cysteine donor on muscular performance.

Abstract

Oxidative stress contributes to muscular fatigue. GSH is the major intracellular antioxidant, the biosynthesis of which is dependent on 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 men, 10 women) were studied presupplementation and 3 mo postsupplementation with either Immunocal (20 g/day) or casein placebo. Muscular performance was assessed by whole leg isokinetic cycle testing, measuring peak power and 30-s 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-s work capacity). Follow-up data on 18 subjects (9 Immunocal, 9 placebo) were analyzed. Both peak power [13 +/- 3.5 (SE) %, P < 0.02] and 30-s work capacity (13 +/- 3.7%, P < 0.03) increased significantly in the Immunocal group, with no change (2 +/- 9.0 and 1 +/- 9.3%) in the placebo group. Lymphocyte GSH also increased significantly in the Immunocal group (35.5 +/- 11.04%, P < 0.02), with no change in the placebo group (-0.9 +/- 9.6%). This is the first study to demonstrate that prolonged supplementation with a product designed to augment antioxidant defenses resulted in improved volitional performance.


Top of Page

https://www.ncbi.nlm.nih.gov/pubmed/10517767

Treatment of obstructive airway disease with a cysteine donor protein supplement: a case report.

Abstract

Oxidant/antioxidant imbalance can occur in obstructive airways disease as a result of ongoing inflammation. Glutathione (GSH) 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 who had obstructive lung disease responsive to corticosteroids, and low whole blood GSH levels. After 1 month of supplementation with a whey-based oral supplement designed to provide GSH precursors, whole blood GSH levels and pulmonary function increased significantly and dramatically. The potential for such supplementation in pulmonary inflammatory conditions deserves further study.
Top of Page

https://www.ncbi.nlm.nih.gov/pubmed/10713031

Nutritional therapy of chronic hepatitis by whey protein (non-heated).

Abstract

In an open study the clinical efficacy of milk serum (whey) protein (Immunocal; cysteine content: 7.6-fold higher than that of casein) isolated from fresh milk and purified without heating was evaluated in 25 patients with chronic hepatitis B or C. 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 similarly given for two weeks prior to the start of the supplement with Immunocal food (induction period) and for four weeks after the end of the supplement with Immunocal food (follow-up period). Serum alanine aminotransferase (ALT) activity was reduced, and plasma glutathione (GSH) levels increased in six and five of eight patients with chronic hepatitis B, respectively, 12 weeks after the start of the supplement with Immunocal food. Serum lipid peroxide levels significantly decreased, and interleukin (IL)-2 levels and natural killer (NK) activity significantly increased. However, there were no significant Immunocal-related changes in 17 patients with chronic hepatitis C. These findings suggest that the long-term supplement with Immunocal alone may be effective for improving liver dysfunctions in patients with chronic hepatitis B.
Top of Page

https://www.ncbi.nlm.nih.gov/pubmed/11508322

Whey protein concentrate (WPC) and glutathione modulation in cancer treatment.

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.
Top of Page

https://www.ncbi.nlm.nih.gov/pubmed/11205219

Enchancing effect of patented whey protein isolate (Immunocal) on cytotoxicity of an anticancer drug.

Abstract

To determine the enhancing effect of a whey protein isolate on the cytotoxicity of a potential anticancer drug, baicalein, the human hepatoma cell line Hep G2 was assigned to grow in different media for four days, and cell growth and apoptosis were investigated. The control group was grown in normal medium; the other three groups were grown in whey protein isolate (Immunocal) medium, baicalein medium, and a combination of Immunocal and baicalein. As indicated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay, survival rate was significantly lower in cells grown in baicalein + Immunocal than in cells grown in baicalein alone. In contrast, there was no significant difference in survival rate of the cells grown in Immunocal. In the investigation of apoptosis, cells grown in baicalein + Immunocal showed a higher phosphatidylserine exposure, lower mitochondrial transmembrane potential, and nearly 13 times more cells undergoing apoptosis than cells grown in baicalein alone. We also demonstrated that Immunocal reduced glutathione (GSH) in Hep G2 cells by 20-40% and regulated the elevation of GSH, 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 associated with the depletion of GSH in Hep G2 cells. This is the first study to demonstrate, in vitro, that Immunocal may function as an adjuvant in cancer treatments.
Top of Page

https://www.ncbi.nlm.nih.gov/pubmed/11525598

Nutriceutical Modulation of Glutathione with a Humanized Native Milk Serum Protein Isolate, Immunocal: Application in Aids and Cancer

S. Baruchel1, G. Viau1, R. Olivier2, G. Bounous3, M.A. Wainberg4
1McGill University – Montreal Children’s Hospital Research Institute, Montreal, Quebec, Canada, 2Pasteur Institute Paris, France, 3Montreal General Hospital, Montreal, Quebec, Canada, 4Jewish General Hospital, Lady Davis Institute, Montreal, Quebec, Canada.

Oxidative Stress in Cancer, Aids, and Neurodegenerative Diseases – Luc Montagnier et Al., (Ed.) Marcel Dekker Inc., New York: 447-461, 1998

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.


Top of Page

The antioxidant system.

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.

Top of Page

https://www.ncbi.nlm.nih.gov/pubmed/12820403

Milk whey protein decreases oxygen free radical production in a murine model of chronic iron-overload cardiomyopathy.

Abstract

BACKGROUND:
Chronic iron overload is a major cause of organ failure worldwide, but its pathogenesis remains to be elucidated.

OBJECTIVES:

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.

METHODS:

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.

RESULTS:

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).

CONCLUSION:

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.
Top of Page

https://www.ncbi.nlm.nih.gov/pubmed/14532942

Molecular pathogenesis and prevention of prostate cancer.

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.
Top of Page

https://www.ncbi.nlm.nih.gov/pubmed/15160993

Improved glutathione status in young adult patients with cystic fibrosis supplemented with whey protein.

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.
Top of Page

https://www.ncbi.nlm.nih.gov/pubmed/15463873

Effects of cysteine donor supplementation on exercise-induced bronchoconstriction.

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 > or =10% in FEV1 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 FEV(1) from 0 wk (-22.6 +/- 12.22%) with TX at 4 (-18.9 +/- 12.89%, P < 0.05) and 8 wk (-16.98 +/- 11.61%, P < 0.05) and significant mean reduction in post-EVH peak falls in FEF(25-75) from 0 wk (-40.6 +/- 15.28%) with TX at 4 (-33.1 +/- 17.11%, P < 0.01) and 8 (-29.7 +/- 17.42%, P < 0.05) wk. No changes in FEV(1) or FEF(25-75) 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.
Top of Page

https://www.ncbi.nlm.nih.gov/pubmed/16177596

Oxidative stress and ageing: is ageing a cysteine deficiency syndrome?

Abstract

Reactive oxygen species (ROS) are constantly produced in biological tissues and play a role in various signalling 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 signalling 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 α (TNF-α), improved immune functions, and increased plasma albumin levels. As all these parameters degenerate 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.
Top of Page

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1569588/

Aberrant insulin receptor signaling and amino acid homeostasis as a major cause of oxidative stress in aging.

Abstract

The mechanisms leading to the increase in free radical-derived oxidative stress in “normal aging” remains obscure. Here we present our perspective on studies from different fields that 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 that normally ensures free amino acid homeostasis during starvation. Autophagy is negatively regulated by the insulin receptor signaling cascade that 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 that were found to have an impact on lifespan in several animal models of aging). In addition, the aging-related decrease in glutathione levels is likely to facilitate certain “secondary” disease-related mechanisms of oxidative stress. Studies on cysteine supplementation show therapeutic promise.
Top of Page

https://www.ncbi.nlm.nih.gov/pubmed/18162053

Cysteine-rich protein reverses weight loss in lung cancer patients receiving chemotherapy or radiotherapy.

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 a 6-month period was 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 > or =3%, Karnofsky status > or =70, and an estimated survival of >3 months. Thirty-five lung cancer patients remained on study at 6 weeks. Overall compliance was not different between treatment arms (42-44% or 13 g/day). The patients treated with the cysteine-rich protein had a mean increase of 2.5% body weight, whereas casein-treated patients lost 2.6% (p = 0.049). Differences in secondary endpoints 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.
Top of Page

https://www.ncbi.nlm.nih.gov/pubmed/18158761

Glutathione augments the activation of cytotoxic T lymphocytes in vivo.

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.
Top of Page

https://www.ncbi.nlm.nih.gov/pubmed/3490430

Oral Tolerability of Cysteine-Rich Whey Protein Isolate in Autism-A Pilot Study

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.
Top of Page

View Article

Children’s Oncology Group (COG) Nutrition Committee.

Abstract

The Children’s Oncology Group (COG) Nutrition Committee was established to further the knowledge of nutrition in children with cancer by education and the 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. This 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.
Top of Page

https://www.ncbi.nlm.nih.gov/pubmed/18064639

Open-labeled pilot study of cysteine-rich whey protein isolate supplementation for nonalcoholic steatohepatitis patients.

Abstract

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 20 g 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.
Top of Page

https://www.ncbi.nlm.nih.gov/pubmed/19638084

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
PRESENTED AT THE INTERNATIONAL CONFERENCE ON AIDS; INT. CONF. AIDS AUG. 7-12, 1994 (Abstract no. 421A)

Abstract

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.


Top of Page

In vitro selective modulation of cellular glutathione by a humanized native milk protein isolate in normal cells and rat mammary carcinoma model.

Abstract

We report the in vitro selective inhibitory activity of a humanized whey protein concentrate IMMUNOCAL on growth of mammary carcinoma cells and Jurkat T cells in comparison to normal peripheral blood mononuclear cells. We relate this inhibitory activity to a selective depletion of intracellular glutathione synthesis. The use of humanized whey protein concentrate as a food supplementation may have direct implication in clinical trial with adjuvant chemotherapy.
Top of Page

https://www.ncbi.nlm.nih.gov/pubmed/8702219

Whey protein concentrate promotes the production of glutathione (GSH) by GSH reductase in the PC12 cell line after acute ethanol exposure.

Abstract

Excessive ethanol consumption may increase the production of reactive oxygen species (ROS), which results in the damage of tissues, especially the neurons and glial cells in the central nervous system (CNS). The purpose of this study is to evaluate the effects of whey protein concentrate (WPC) on the glutathione (GSH) status after acute ethanol exposure in the pheochromocytoma (PC12) cell line. In this study, we assayed the cell viability, the percentage of lactate dehydrogenase released (% LDH released), the level of GSH, and the activity of GSH reductase (GRx). The results showed that with the supplement of WPC, the cell viability displayed no significant difference after acute exposure of ethanol in groups with or without ethanol treatment. The ethanol-induced cytotoxicity showed a slight decrease ,and the level of GSH showed a significant increase. The activity of GRx significantly increased when 0.1, 10mg/ml of WPC was supplied. In conclusion, these results suggest that WPC in a moderate concentration should be a precursor agent to promote the production of GSH and will enhance the antioxidant capacity in the PC12 cell line.
Top of Page

https://www.ncbi.nlm.nih.gov/pubmed/16360258

Effects of alcohol-induced human peripheral blood mononuclear cell (PBMC) pretreated whey protein concentrate (WPC) on oxidative damage.

Abstract

Excessive alcohol consumption can induce apoptosis in a variety of tissues and influence the antioxidant status in peripheral blood mononuclear cells (PBMC). This paper investigates the effects of whey protein concentrate (WPC) pretreated in PBMC on the apoptosis and antioxidant status after the treatment of alcohol. The results show that the percentages of apoptotic cells in the alcohol-treated group were higher than those in the group without alcohol treatment. Additionally, there was higher glutathione (GSH) peroxidase (GPx) activity when the PBMC were treated with 300 mg/dL of alcohol. With regard to the activity of GSH reductase (GRx), there was higher activity in the group pretreated with WPC than in the group with the treatment of alcohol only. On the contrary, the levels of GSH were reduced after the treatment of alcohol, but there was a higher level of GSH in the group pretreated with WPC. In this study, it was found that the increased level of GSH in PBMC might not be attributed to the effect of GRx because there was still a higher level of GSH in the group with the treatment of WPC and BCNU (a GRx inhibitor) in this study. The results indicated that PBMC pretreated with WPC might ameliorate alcohol-induced effects such as imbalance of the antioxidant status.
Top of Page

https://www.ncbi.nlm.nih.gov/pubmed/18700777

Effects of whey protein concentrate (WPC) on the distributions of lymphocyte subpopulations in rats with excessive alcohol intake.

Abstract

To investigate the effects of whey protein concentrate (WPC) on antioxidant statuses and the lymphocyte subpopulations in the rats with alcohol intake, the antioxidant statuses in the peripheral blood (PB) and the lymphocyte subpopulations in the PB, spleen, and bone marrow (BM) of the rats fed with WPC (0.334 g/kg) and alcohol (6 g/kg) for 3 months were analyzed. Results showed that the effects of WPC on the glutathione peroxidase and glutathione in the PB, the T and B cells in the spleen, and the B cells in the BM were more apparent in the rats with alcohol intake; however, they are not apparent in the controls. Taken together, our results indicated that the immunity of rats might be enhanced by the increased antioxidant ability after WPC supplementation and the effects of WPC on the lymphocyte subpopulations were mainly in the spleen and BM and not in the PB.
Top of Page

https://www.ncbi.nlm.nih.gov/pubmed/21121609

Psoriasis Improvement in Patients Using Glutathione-enhancing, Nondenatured Whey Protein Isolate: A Pilot Study.

Abstract

BACKGROUND:
Psoriasis is a common autoimmune disease with enhanced systemic inflammation and heightened levels of oxidative stress. Glutathione is the major antioxidant in human cells.

OBJECTIVES:
To determine if a nondenatured bioactive whey protein isolate previously demonstrated to increase glutathione levels can clinically improve patients with psoriasis vulgaris.

METHODS:
A single site, prospective, non-blinded trial. Seven patients with psoriasis were recruited to take a nondenatured bioactive whey protein isolate, 20g orally per day, in addition to their current treatments, if any. Psoriasis Area and Severity Index scores and photographs were taken at baseline and monthly for three months.

RESULTS:
Patients with psoriasis were found to have a beneficial clinical improvement, whether they were on existing topical therapy, narrowband ultraviolet B, or no other treatment.

CONCLUSION:
The positive preliminary outcomes from this pilot study suggest a randomized, double-blind, clinical trial would be worthwhile in evaluating whether this protein isolate would result in statistically significant improvement for patients with psoriasis.
Top of Page

https://www.ncbi.nlm.nih.gov/pubmed/24155989

Immunocal® and preservation of glutathione as a novel neuroprotective strategy for degenerative disorders of the nervous system.

Abstract

Oxidative stress and glutathione (GSH) depletion are both recognized as significant contributors to the pathogenesis of many devastating neurodegenerative diseases. In particular, mitochondrial dysfunction leads to the aberrant production and accumulation of reactive oxygen species (ROS), which are capable of oxidizing key cellular proteins, lipids, and DNA, ultimately triggering cell death. In addition to other roles that it plays in the cell, GSH functions as a critical scavenger of these ROS. Therefore, GSH depletion exacerbates cell damage due to free radical generation. Strategies that increase or preserve the levels of intracellular GSH have been shown to act in a neuroprotective manner, suggesting that augmentation of the available GSH pool may be a promising therapeutic target for neurodegeneration. This review discusses the capacity of a cystine-rich, whey protein supplement (Immunocal®) to enhance the de novo synthesis of GSH in neurons, and highlights its potential as a novel therapeutic approach to mitigate the oxidative damage that underlies the pathogenesis of various neurodegenerative diseases. Additionally, this review discusses various patents from 1993 to 2012 both with Immunocal® and other methods that modulate GSH in neurodegeneration.
Top of Page

https://www.ncbi.nlm.nih.gov/pubmed/22742422

Therapeutic Antioxidants for Neurodegenerative Disease

Abstract

The aberrant production of reactive oxygen species (ROS) within a cell can cause significant oxidative damage to key cellular
proteins, lipids, and DNA. Harmful free radical species like ROS can be generated intrinsically via inadvertent “leakage”
from the mitochondrial electron transport chain or by oxidant-generating enzymatic systems like NADPH oxidase, xanthine
oxidase, glucose oxidase, or nitric oxide synthase. Alternatively, noxious free radicals can be generated by extrinsic sources
such as toxins or reactive inflammatory cells. Regardless of their source, ROS and other free radical species must be scavenged
by intracellular antioxidant systems to protect the cell from oxidative damage and consequent cell death. To this end, the cell
has developed a large repertoire of antioxidant defense mechanisms that are normally able to keep ROS in check; however,
during many disease states these antioxidant defenses are often overwhelmed and the cell succumbs to oxidative stress. This
certainly appears to be the case in many types of neurodegenerative disease including Alzheimer’s disease, Parkinson’s disease,
Huntington’s disease, and amyotrophic lateral sclerosis, to name a few. For each of these disorders, oxidative stress is a significant
factor in the neuronal death underlying disease pathogenesis [1]. In addition, oxidative stress is hypothesized to play a substantial
role in aging which is a major risk factor for neurodegeneration [2]. Thus, it is not surprising that strategies either to
bolster endogenous antioxidant defenses or to provide exogenous free radical scavengers are currently under intense investigation
as potential therapies for neurodegeneration.
Top of Page

https://www.ncbi.nlm.nih.gov/pubmed/22857712
View Article

Bringing evidence to complementary and alternative medicine in children with cancer: Focus on nutrition-related therapies.

Abstract

Children with cancer frequently use complementary and alternative medicine (CAM), especially in conjunction with conventional therapy. Dietary supplements are a commonly used CAM modality, with the prevalence of supplement use ranging from 35% to 50% of children with cancer in surveys completed in the United States. Less is known about the use of dietary supplements in developing countries. The evidence for some dietary supplements providing some benefit to children with cancer is reviewed. Preliminary studies have shown that antioxidant status may affect chemotherapy tolerance in children with acute lymphoblastic leukemia. Other supplements, including TRAUMEEL S, glutamine, vitamin E, Immunocal, colostrum, and probiotics, may help to reduce gastrointestinal toxicities of chemotherapy and radiation. However, more definitive evidence is needed. Most dietary supplements have not been tested adequately to determine their safety and efficacy, with even less understood about their potential interactions with conventional chemotherapy and radiation. With the greater use of dietary supplements by patients with cancer, increasing scientific attention is being paid to the investigation of these therapies. But research on dietary supplements is complex and usually more difficult than that on conventional medications. Strong research designs are critical in obtaining information that will ultimately influence clinical practice and public awareness.
Top of Page

https://www.ncbi.nlm.nih.gov/pubmed/18064645

Effect of cysteine-rich whey protein (immunocal®) supplementation in combination with resistance training on muscle strength and lean body mass in non-frail elderly subjects: a randomized, double-blind controlled study.

Abstract

OBJECTIVES:
The purpose of the present study was to examine the effect of a cysteine-rich whey protein (Immunocal®) supplementation in combination with resistance training on muscle strength and lean body mass (LBM) in elderly individuals. We hypothesized that the cysteine-rich whey protein (Immunocal®) group would experience a greater increase in muscle strength and lean body mass versus the control group (casein).

DESIGN:
Randomized double-blind controlled intervention study.

SETTING:
Institut de Recherches Cliniques de Montréal in Montreal, Canada.

PARTICIPANTS:
Ninety-nine non-frail elderly subjects were recruited.

INTERVENTION:
Participants were randomly assigned into two groups. The experimental group received a cysteine-rich whey protein isolate (Immunocal®) (20 g/day) and the control group received casein (20 g/day) during a 135-day period. In addition, both groups performed the same resistance training program (3 times per week).

MEASUREMENTS:
Body composition (DXA) and muscle strength (leg press) were measured.

RESULTS:
Of the 99 recruited participants, 84 completed the 135-day study period. Of these, 67 subjects (33 in the casein group and 34 in the Immunocal® group) complied and used at least 80 % of the study product and completed at least 80 % of their training sessions. Results in this selected group show an increase in all three muscle strength variables (absolute, normalized by BW and by LBM) by 31.0 %, 30.9 % and 30.0 %, respectively in the casein group as well as 39.3 %, 39.9 % and 43.3 %, respectively in the Immunocal® group after the intervention (p < 0.05). The increases in muscle strength favored Immunocal® versus casein by approximately 10 % when expressed in kg per kg BW and in kg per kg LBM (p < 0.05). No significant changes were found between pre-and-post intervention in both groups for total LBM.

CONCLUSIONS:
Our findings showed increases in muscle strength in both groups after resistance training, however, significant additional increases were observed in muscle strength with the addition of a cysteine-rich whey protein (Immunocal®) versus casein.
Top of Page

https://www.ncbi.nlm.nih.gov/pubmed/25923482

Prehabilitation versus rehabilitation: a randomized control trial in patients undergoing colorectal resection for cancer.

Abstract

BACKGROUND:
The preoperative period (prehabilitation) may represent a more appropriate time than the postoperative period to implement an intervention. The impact of prehabilitation on recovery of function al exercise capacity was thus studied in patients undergoing colorectal resection for cancer.

METHODS:
A parallel-arm single-blind superiority randomized controlled trial was conducted. Seventy-seven patients were randomized to receive either prehabilitation (n = 38) or rehabilitation (n = 39). Both groups received a home-based intervention of moderate aerobic and resistance exercises, nutritional counseling with protein supplementation, and relaxation exercises initiated either 4 weeks before surgery (prehabilitation) or immediately after surgery (rehabilitation), and continued for 8 weeks after surgery. Patients were managed with an enhanced recovery pathway. Primary outcome was functional exercise capacity measured using the validated 6-min walk test.

RESULTS:
Median duration of prehabilitation was 24.5 days. While awaiting surgery, functional walking capacity increased (≥ 20 m) in a higher proportion of the prehabilitation group compared with the rehabilitation group (53 vs. 15%, adjusted P = 0.006). Complication rates and duration of hospital stay were similar. The difference between baseline and 8-week 6-min walking test was significantly higher in the prehabilitation compared with the rehabilitation group (+23.7 m [SD, 54.8] vs. -21.8 m [SD, 80.7]; mean difference 45.4 m [95% CI, 13.9 to 77.0]). A higher proportion of the prehabilitation group were also recovered to or above baseline exercise capacity at 8 weeks compared with the rehabilitation group (84 vs. 62%, adjusted P = 0.049).

CONCLUSION:
Meaningful changes in postoperative functional exercise capacity can be achieved with a prehabilitation program.
Top of Page

https://www.ncbi.nlm.nih.gov/pubmed/25076007

Prehabilitation with Whey Protein Supplementation on Perioperative Functional Exercise Capacity in Patients Undergoing Colorectal Resection for Cancer: A Pilot Double-Blinded Randomized Placebo-Controlled Trial.

Abstract

BACKGROUND:
A previous comprehensive prehabilitation program, providing nutrition counseling with whey protein supplementation, exercise, and psychological care, initiated 4 weeks before colorectal surgery for cancer, improved functional capacity before surgery and accelerated functional recovery. Those receiving standard of care deteriorated. The specific role of nutritional prehabilitation alone on functional recovery is unknown.

OBJECTIVE:
This study was undertaken to estimate the impact of nutrition counseling with whey protein on preoperative functional walking capacity and recovery in patients undergoing colorectal resection for cancer.

DESIGN:
We conducted a double-blinded randomized controlled trial at a single university-affiliated tertiary center located in Montreal, Quebec, Canada. Colon cancer patients (n=48) awaiting elective surgery for nonmetastatic disease were randomized to receive either individualized nutrition counseling with whey protein supplementation to meet protein needs or individualized nutrition counseling with a nonnutritive placebo. Counseling and supplementation began 4 weeks before surgery and continued for 4 weeks after surgery.

MAIN OUTCOME MEASURE:
The primary outcome was change in functional walking capacity as measured with the 6-minute walk test. The distance was recorded at baseline, the day of surgery, and 4 weeks after surgery. A change of 20 m was considered clinically meaningful.

RESULTS:
The whey group experienced a mean improvement in functional walking capacity before surgery of +20.8 m, with a standard deviation of 42.6 m, and the placebo group improved by +1.2 (65.5) m (P=0.27). Four weeks after surgery, recovery rates were similar between groups (P=0.81).

CONCLUSION:
Clinically meaningful improvements in functional walking capacity were achieved before surgery with whey protein supplementation. These pilot results are encouraging and justify larger-scale trials to define the specific role of nutrition prehabilitation on functional recovery after surgery.
Top of Page

https://www.ncbi.nlm.nih.gov/pubmed/26208743

Biochemical and clinical effects of Whey protein supplementation in Parkinson’s disease: A pilot study.

Abstract

BACKGROUND:
Parkinson’s disease (PD) is an oxidative stress-mediated degenerative disorder. Elevated plasma homocysteine (Hcy) is frequently found in the levodopa-treated PD patients, is associated with disease progression and is a marker of oxidative stress. Whey protein is a rich source of cysteine, and branched-chain amino acids (BCAA). It has been shown that supplementation with Whey protein increases glutathione synthesis and muscle strength.

OBJECTIVES AND METHODS:
In this study, we conducted a placebo-controlled, double-blind study (NCT01662414) to investigate the effects of undenatured Whey protein isolate supplementation for 6months on plasma glutathione, plasma amino acids, and plasma Hcy in PD patients. Clinical outcome assessments included the unified Parkinson’s disease rating scale (UPDRS) and striatal L-3,4-dihydroxy-6-(18)F-fluorophenylalanine (FDOPA) uptake were determined before and after supplementation. 15 patients received Whey protein, and 17 received Soy protein, served as a control group.

RESULTS:
Significant increases in plasma concentration of reduced glutathione and the ratio of reduced to oxidized glutathione were found in the Whey-supplemented patients but not in a control group. This was associated with a significant decrease of plasma levels of Hcy. The plasma levels of total glutathione were not significantly changed in either group. Plasma BCAA and essential amino acids (EAA) were significantly increased in the Whey-supplemented group only. The UPDRS and striatal FDOPA uptake in PD patients were not significantly ameliorated in either group. However, significant negative correlation was observed between the UPDRS and plasma BCAA and EAA in the pre-supplemented PD patients.

CONCLUSION:
This study is the first to report that Whey protein supplementation significantly increases plasma reduced glutathione, the reduced to oxidized glutathione ratio, BCAAs and EAAs in patients with PD, together with a concomitant significant reduction of plasma Hcy. However, there were no significant changes in clinical outcomes. Long-term, large randomized clinical studies are needed to explore the benefits of Whey protein supplementation in the management of PD patients.
Top of Page

https://www.ncbi.nlm.nih.gov/pubmed/27423583