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  1. #1
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    Default Undenatured Whey Isolate and it's role in health and immunity via Glutathione product

    Initially I was going to write an article on the use of undenatured whey proteins (concentrate/isolate), however I've sucumbed to time restraints at the moment via work and 5 kids. Yeah, that's right, 5 kids!

    So, with my anxiousness and all, a few hours of free time over the weekend, I've decided to get posting some information and studies to get the discussion moving forward now, rather than later. Especially with the state of world governments hoopla and all the H1N1 mind fucking going on.

    We all (athletes/bodybuilders) know the importance of protein, dietary and in supplemental form, to combat the catabolic effect of diet and exercise, weight training etc. as well to stimulate protein synthesis and assist in muscle tissue growth. But I've noticed that most of us(generically) are not aware of the potential health benefits outside of muscle growth and blunting a catabolic state. In my opinion, we should all learn and pay attention to this, because of increasing disease and ailments, and why not increase our health overall, by taking a supplement that we might take anyhow? Sounds logical to me.

    Of course, sometimes we do not discriminate between the types of protein we use, especially though supplementation. Often opting for whey protein concnetrate becausse of it's low price and efficiency for producing response in regards to lean mass accruel and recovery. But is it really worth the price difference to purchase undenatured proteins? Hell yeah, at least in my opinion.

    Whey protein concentrate is of poor biological effects do to the denatured state of being produced with heat. Whey miscrofractions are delicate and damaged by heat. CMF (cold processed cross flow microfiltered) protein is the way to go, whether it's whey concnetrate or whey isolate. This allows the immune stimulating effects of the microfractions to remain intact, and this what seperates the effectiveness of proteins and the immune system.

    Whether it be whey protein concentrate or whey isolate (undenatured), I prefer isolate because of it's higher protein and microfraction content. Is this important? Yeah, but it's not life or death, because they both acheive the same response, just undenatured whey isolate will do so more efficiently.


    So, more discussion on this later. I'll post some reference material and some studies on undenatured whey proteins...

    Feel free to chime in with thoughts and/or questions.

  2. #2
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    J Gastroenterol Hepatol. 2009 Jun;24(6):1045-50.
    Open-labeled pilot study of cysteine-rich whey protein isolate supplementation for nonalcoholic steatohepatitis patients.

    Chitapanarux T, Tienboon P, Pojchamarnwiputh S, Leelarungrayub D.
    Division of Gastrohepatology, Department of Medicine, Chiang Mai University, Thailand. [email protected]
    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.

    PMID: 19638084 [PubMed - in process]

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    Med Sci Sports Exerc. 2005 Sep;37(9):1468-73.
    Effects of cysteine donor supplementation on exercise-induced bronchoconstriction.

    Baumann JM, Rundell KW, Evans TM, Levine AM.
    Human Performance Laboratory, Marywood University, Scranton, PA 18509, USA.
    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.

    PMID: 16177596 [PubMed - indexed for MEDLINE

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    J Med Food. 2005 Fall;8(3):337-42.
    Effect of different hydrolysates of whey protein on hepatic glutathione content in mice.

    Pacheco MT, Sgarbieri VC.
    Food Chemistry and Applied Nutrition Center-Institute of Food Technology, Campinas, São Paulo, Brasil. [email protected]
    This study was designed to compare the effects of diets prepared with enzymatic hydrolysate of a whey protein concentrate (WPC) by pancreatin, protamex (Novo Nordisk, Bagsvaerd, Denmark), and alcalase proteases on the hepatic glutathione content in mice. The undenatured WPC was produced in a pilot plant by membrane technology (microfiltration/diafiltration) after separation of the casein clot through a conventional process. All three hydrolysates with 20% degree of hydrolysis showed an amino acid profile similar to WPC. Male A/J mice were fed on diets containing 20% WPC or hydrolysates. Commercial casein was used as a reference protein in the biological assays. The glutathione content was determined after liver extraction through high-performance capillary electrophoresis. WPC and its pancreatin and protamex hydrolysates showed higher ability to stimulate liver glutathione synthesis than alcalase hydrolysate. This difference was probably related to an amino acid sequence in the peptides that were formed during hydrolysis of whey proteins. Commercial casein and WPC alcalase hydrolysate produced lower stimulation of liver glutathione synthesis (7.09 and 5.66 micromol/g of wet weight) compared with WPC and pancreatin and protamex hydrolysates (8.72, 8.71, and 8.45 micromol/g of wet weight, respectively). These results indicate that the hydrolysates obtained by treatment with pancreatin and protamex are good sources of peptides with activity to stimulate glutathione synthesis.

    PMID: 16176144 [PubMed - indexed for MEDLINE]

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    Clin Invest Med. 1993 Jun;16(3):204-9.
    Whey proteins as a food supplement in HIV-seropositive individuals.

    Bounous G, Baruchel S, Falutz J, Gold P.
    Department of Surgery, Montreal General Hospital, Quebec.
    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.

    PMID: 8365048 [PubMed - indexed for MEDLINE]

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    Clin Invest Med. 1991 Aug;14(4):296-309.
    The biological activity of undenatured dietary whey proteins: role of glutathione.

    Bounous G, Gold P.
    Department of Surgery, Montreal General Hospital Research Institute, Quebec.
    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.

    PMID: 1782728 [PubMed - indexed for MEDLINE]

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  7. #7
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    good stuff natron. At first i was skeptical of the value. I have a question, however.

    Cant you supplement with glutathione instead? Glutathione is basically a polypeptide with repeated cysteines (which get oxydized with exessive heat).

  8. #8
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    Quote Originally Posted by Dr Pangloss View Post
    good stuff natron. At first i was skeptical of the value. I have a question, however.

    Cant you supplement with glutathione instead? Glutathione is basically a polypeptide with repeated cysteines (which get oxydized with exessive heat).
    Unfortunately you can't. You can buy reduced glutathione, but it won't reach the cells or stimulate glutathione synthesis. Oral glutathione products a very poor at best at raising cellular levels. Garlic extract, milk thistle can raise levels minutely, but it is hardly beneficial. NAC is also a bust, however injectible NAC has been used to treat acetaminophen overdoses, and is proven to raise intracellular glutathione levels, but that doesn't really help bodybuilders or athletes as it's not readily available.

    I'll unput more on this as we go along, especially in terms of avoiding sickness, over training etc.

    The events that really led me to undenatured protein was dealing with terminally ill cancer patients. I've only done this 3-4 times, however, these people are still living almost 6 years later. So, I am quite fascinated with this supplement, and rightfully so. Look at all the petty disease, flu etc. Simply switching to an undenatured whey protein can dramatically increase your health and well being, while increasing recovery and building muscle! lol

    Anyhow,

    and to everyone else who checks this out, I have no affiliation with any supplement company at all, just to get that out of the way!

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    Here is a link to an excellent product, with studies and descriptions of how lactoferin (from undenatured whey), will stimulate the immune system and has powerful anti-cancer effects. This product is made by AOR, and they are definately not cheap, but since gaining my R.N.C.P. degree, they make some of the best supplements I've ever seen. Much more like a pharmaceutical company rather than a company just throwing around compounds, but anyhow, take a look, and the studies are in there as well.

    http://www.aor.ca/html/products.php?id=124

  10. #10
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    for Dr. P

    NAC- oral n-acetyl cysteine is rather ineffective at raising intracellular glutathione levels because it's bioavailability is very low. This is a by product of first pass motabolism through the liver which basically cleaves the molecules into smaller molocules to create different compounds. Not only that, but the half life of oral NAC is somewhere around 1 hour, which would make it a pain in the ass to see any benefits from.

    oral glutathione basically suffers the same fate as NAC, it's low bioavailability just doesn't allow an effective dose to reach cells.

    undenatured protein is more effective because it supplies the donors allowing the body to make glutathione on it's own, thus depleted stores within the body are topped up, and allowed to maintain normal levels, especially in those who are sick, suffering from illness or disease, or those who are physically taxing their bodies ie athletes/bodybuilders.

  11. #11
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    some other applications for increasing glutathione..

    • Relief from the symptoms of chronic bronchitis.
    • Heavy metal chelation.
    • Precursor to glutathione.
    • Anti-mucus in the lungs.
    • Acetaminophen overdose.
    • AIDS complications.
    • Anti-HIV activity in-vitro.
    • Cell-protective effect when dapsone (which is cytotoxic) is used to treat Pneumocystis carinii pneumonia (PCP) in AIDS.
    • Liver detoxification

    There are also some interesting reads I'm looking for in regards to GSH improving mental conditions involving glutamate activity. So, it could potentially help with schizophrenia, ADD, and ADHD (although fish oils are bang on for these applications).

    I've also seen elimination of allergies through undenatured whey supplementation as well.

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    J Cyst Fibros. 2003 Dec;2(4):195-8.
    Improved glutathione status in young adult patients with cystic fibrosis supplemented with whey protein.

    Grey V, Mohammed SR, Smountas AA, Bahlool R, Lands LC.
    The Department of Pathology and Molecular Medicine, McMaster Division, Hamilton Health Sciences, Hamilton, Ontario, Canada.
    Erratum in:

    • J Cyst Fibros. 2004 Mar;3(1):62.

    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. Copyright 2003 European Cystic Fibrosis Society

    PMID: 15463873 [PubMed - indexed for MEDLINE]

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    Nutr Cancer. 2000;38(2):200-8.
    Enchancing effect of patented whey protein isolate (Immunocal) on cytotoxicity of an anticancer drug.

    Tsai WY, Chang WH, Chen CH, Lu FJ.
    Department of Biochemistry, College of Medicine National Taiwan University, Taipei, ROC.
    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.

    PMID: 11525598 [PubMed - indexed for MEDLINE]

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    J Med. 2000;31(5-6):283-302.
    Nutritional therapy of chronic hepatitis by whey protein (non-heated).

    Watanabe A, Okada K, Shimizu Y, Wakabayashi H, Higuchi K, Niiya K, Kuwabara Y, Yasuyama T, Ito H, Tsukishiro T, Kondoh Y, Emi N, Kohri H.
    Third Department of Internal Medicine, Toyama Medical and Pharmaceutical University, Toyama, Japan.
    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.

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    J Appl Physiol. 1999 Oct;87(4):1381-5.
    Effect of supplementation with a cysteine donor on muscular performance.

    Lands LC, Grey VL, Smountas AA.
    Division of Respiratory Medicine, McGill University Health Centre-Montreal Children's Hospital, Montreal, Quebec, Canada H3H 1P3. [email protected]
    Erratum in:

    • J Appl Physiol 2000 Jan;88(1):followi.

    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.

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