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Glutathione(GSH) and Undenatured Whey Protein in HIV-AIDS

Copyright © 2002 1Whey2Health
Reproduction Prohibited


How do Glutathione (GSH) and whey protein help in HIV-AIDS ?

Glutathione can inhibit HIV replicationFree radicals have been linked to much of the immune system destruction caused by HIV.

A wide range of antioxidants have been shown to protect immune function, and nutrients that maintain cellular levels of glutathione are especially important in preventing or slowing the progression of HIV infection.


HIV depletes the cells of Glutathione

It is now widely understood that AIDS is associated with a deficiency of glutathione that leads to the generation of enormous levels of oxidative stress that damage and kill otherwise-healthy cells throughout the body (1).

HIV has been shown to induce cellular depletion of glutathione. Low glutathione may be especially important in HIV, as there is evidence that the Tat protein produced by this virus can abnormally reduce glutathione levels (2).

This is associated with free radical injury to numerous immune-system components. T-helper lymphocytes require adequate levels of glutathione to function normally, and HIV induces oxidative stress that depletes T-helper cells of glutathione (3).

Numerous studies reveal that the lack of glutathione causes lymphocytes to become weak in their immunological "efficiency," thereby contributing to the immune cell impairment characteristic of AIDS (4).


Glutathione (GSH) can protect the immune system from oxidative stress

Numerous findings have supported the theory that oxidative stress is critical to the pathogenesis of HIV infection. (5).

When your body comes in contact with a pathogen or disease organism, it stimulates the development of an immune response. This oxygen-requiring process produces free radicals as the by-products of metabolism, and depletes the glutathione (GSH) in lymphocytes (mononuclear or white blood cells responsible for mounting an immune response).

The intact immune system appears to require a delicate balance between pro-oxidant and antioxidant conditions, maintained by a limited and well-regulated supply of cysteine. This balance is obviously disturbed in HIV infection and may contribute to the pathogenesis of AIDS. (26)

Glutathione...is the major defense of CD4 T-cells cells against oxidative stress. Depletion of intracellular GSH (Glutathione) has also been shown to decrease the proportion of CD8+ cells (i.e. increases the CD4/CD8 ratio) and inhibit cytotoxic T lymphocyte (CTL) activity (5).

Oxidative stress may lead to enhanced HIV replication in infected cells and may also aggravate the immunodeficiency by reduction of cellular immunity and possibly by increased programmed cell death (apoptosis) of lymphocytes (6).

This suggests that supplementation with nutrients to boost cellular glutathione is crucial to protect against a primary mechanism by which HIV destroys immune function.

Undenatured whey protein provides the components that rapidly replinish the glutathione (GSH) in lymphocytes during this GSH-depleting development of the immune response. Less hampered by oxyradicals, the lymphocyte can thus fully react with an optimal immune response to the disease organism (or antigenic stimulus).

Oxidative stress has also been implicated in HIV-related muscle wasting and weight loss, as well as dementia and neuropathy. It may also play an important role in the genesis of cellular DNA damage and, in this context, may be related to HIV-associated malignancies and disease progression (7).


Glutathione (GSH) inhibits HIV replication and decreases viral load

High levels of cellular glutathione severely limit any virus or bacteria's ability to enter cells and replicate. The infection is subsequently flushed from the system by normal means, which reduces viral load.

A number of studies have shown that high levels of glutathione in mononuclear cells can inhibit HIV replication. Glutathione (GSH) has been shown to interfere with late stages of virus replication (8).

Glutathione was also shown to inhibit the reverse transcriptase (RT) process of HIV-1(9), and to inhibit the expression of induction of HIV-1 (p-24) antigenic proteins required to form the viral coat. (10).

Clinical data and the in vitro demonstration that undenatured whey protein inhibits the HIV virus while increasing GSH synthesis strongly suggest that an antagonistic relation exists between the virus and cellular GSH (11).

Undenatured whey protein was also seen to inhibit the formation of synctia (the cellular "bridges" that allow the virus to be transmitted between immune cells), thereby preventing transmission of the virus between infected and non-infected cells (12).


Replenishing cysteine can boost non-specific immune responses

HIV-infected persons at all stages of the disease have, on the average, decreased plasma cystine and cysteine and decreased intracellular glutathione levels.

There is evidence to suggest that the HIV-induced cysteine deficiency is not only responsible for the 'cellular dysfunction' but also for the abnormal activation which is exemplified by the lymphadenopathy syndrome and abnormal antibody production. (25)

Macrophages - the scavengers of the immune system - are another component of the immune system which relies on glutathione. These large immune cells protect the body by swallowing and destroying foreign particles and cancer cells.

The production of a substance called leukotriene C by macrophages is essential for them to reach invading organisms. When glutathione levels are low, the macrophages' production of leukotriene C is inhibited, resulting in diminished macrophage function.

Clinical trials have shown that the impairment of immunological functions in HIV positive patients results at least partly from cysteine deficiency (13). HIV-induced cysteine depletion is a novel mechanism by which a virus destroys the immune defense of the host and escapes immune elimination.

Supplementation with a "cysteine-delivery system" could replenish the body's requirements of cysteine and reconstitute immune function.

Glutathione has also been shown to enhance the movement (locomotion) of white blood cells called neutrophils to the site of injury or infection and decrease the number of bacterial colonies present there, resulting in improved survival. (14).

Non-specific immune responses are important in the immune system's defenses against opportunistic pathogens.


Higher glutathione levels can improve survival in HIV-AIDS

Studies showing that low GSH levels both promote HIV expression and impair T cell function suggested a link between GSH depletion and HIV disease progression. GSH deficiency has been shown, in numerous studies, to be a key determinant of survival in HIV disease.

A study by Stanford University found that for persons with a CD4 count under 200, an abnormally low level of glutathione - inside CD4 T-cells in the blood - was remarkably predictive of poor survival. The researchers at Stanford showed that those who have lower levels of glutathione inside cells suffer faster progression. (15)

Low glutathione levels in CD4 T-cells mean increased risk of death. The study "provides the first clear indication that GSH deficiency plays a pivotal role in determining how quickly the final stages of HIV disease progress." Clinical trials assessing impact of NAC administration on long-term HIV patient survival are the next logical step in research on the subject. (15)

Supplementation with whey proteins was also shown to persistently increase plasma glutathione levels in patients with advanced HIV-infection. It is possible that this "biochemical efficacy" of whey proteins may translate into a more favourable course of the disease (16).


Undenatured whey protein improves muscle wasting, weight loss and fatigue

Many people living with HIV/AIDS (PHAs) experience muscle loss or wasting. This leads to weakness, weight loss, fatigue and thinning of muscular areas of the body. Muscle wasting in HIV is still not well understood, but it has been linked to abnormally low cysteine levels and loss of sulfur.

Abnormally low plasma cystine levels have been found in the late asymptomatic stage of HIV infection and several other diseases associated with progressive loss of skeletal muscle mass (4). The peripheral tissue was confirmed as the site of massive cysteine loss in HIV infection (Breitkreutz R et al.)

Whey, a component of milk, is a popular diet supplement among AIDS patients because it improves weight gain and provides a protein-rich energy boost while containing little lactose. Whey protein, because of its "biological efficacy," is an easily digestible source of protein.

A recent open label trial was conducted by Louisa Pacheco, M.D. and her colleagues on the therapeutic use of an undenatured whey protein with HIV/AIDS patients at the Tidewater AIDS Crisis Task Force in Norfolk, Virginia. (18)

The AIDS patients who were on the bioactive-cysteine rich nutraceutical, gained an average of 11.9 lbs in 8 weeks. In contrast, the 20 matched non-participating patients experienced an average weight loss of 8.5 lbs and remained non-adherent with anti-retroviral therapy.

In a pilot study, whey protein was shown to improve the nutritional status of children with AIDS and wasting syndrome (19).

One study in PHAs has shown that weight returned to healthier levels after three months of whey protein supplementation. In another study combining exercise, anabolic steroids, nutritional counselling and whey protein, a significant increase in body cell mass (a measure of muscle tissue) was seen.

Many anecdotal reports do tell of gains in muscle mass in PHAs taking whey protein. According to the American buyers' club DAAIR (Direct Access Alternative Information Resources), a number of clients taking whey protein and glutamine have gained lean muscle mass and experienced improvements in their symptoms of fatigue.

In a small pilot study conducted by Dr Bounous and others with HIV-seropositive men, there was a dramatic rise in the levels of GSH in the mononuclear cells of all the study participants, and most participants reached ideal bodyweight.(20)

The increase in bodyweight is as important as the improvement in GSH status because a loss in bodyweight is strongly related to higher morbidity in AIDS patients and a decreased ability to fight off opportunistic infections. (21,22)


Undenatured whey protein regulates digestive function and improves adherence to HAART in PHAs

Glutathione plays an important role in maintaining cellular integrity throughout the body, including the epithelial lining of the intestines. In AIDS patients, chronic inflammation and elevated levels of cytokines seem to be associated with reduced levels of glutathione (GSH) (23).

Part of HIV disease is not just the virus, but the damage done to tissues by an overactive inflammatory response. The intestinal impairment caused by glutathione deficiency often manifests as inflammatory bowel disease, a common problem in AIDS patients that prevents effective absorption of vital nutrients into the body (24).

Undenatured whey protein by some unknown mechanism, appears not only to inhibit wasting syndrome but also to stop the life-threatening diarrhea that AIDS patients so often develop. The removal of lactose may be a particular advantage for PHAs, who are often lactose intolerant.

In a recent open label trial patients taking whey protein achieved significant reduction in gastrointestinal side effects (diarrhea, nausea, vomiting, impaired appetite), as well as improved energy levels.

Additionally, they were able to adhere to their HAART medications as prescribed, which they had previously been unable to do. In fact, patients using whey protein became 100% adherent to HAART by the end of the 8- week trial. (18)


Undenatured whey protein is a safe, effective way to provide glutathione precursors to PHAs

Although a healthy diet is the best way to insure proper nutrient intake, people with HIV frequently have depleted levels of many important vitamins and antioxidants, and such individuals may well require additional supplementation.

Cysteine and glutathione supplements are mainly broken down in the gut, are poorly absorbed into the bloodstream, and increase cell glutathione only marginally. Even with intravenous administration, these drugs do not significantly increase tissue glutathione levels, and have side-effects and toxicity that severely limits their usefulness in the treatment of chronic disease.

Pharmaceutical-grade preparations such as N-acetyl-cysteine (NAC) have dose-limiting toxic profiles, significant side effects, and a relatively short half-life. If the liver is in a weakened state, it may not be able to be convert NAC to glutathione. Taking NAC under these conditions may further suppress lymphocyte functions.

But the cysteine=cysteine dipeptide called cystine in undenatured whey protein enters the blood with no digestion, and donates two cysteine molecules in the cells, where they are used to create glutathione.

"Unlike specific antiretroviral drugs which may induce mutation, hence resistance of the virus to therapy, the normalization of the the lymphocytic glutathione levels and redox status through a cysteine selivery system, represents a totally different approach through which the natural cellular defense system is boosted and against which the virus cannot apparently build up resistance by mutation." - Dr. Gustavo Bounous

However, as Dr. Bounous is clear to point out, he does not see whey protein concentrate as an alternative to traditional treatments, but as a very effective adjunct to traditional therapies for a wide range of diseases.

Most people with AIDS suffer from malnutrition due to massive doses of anti-viral drugs - if they don’t eat, their bodies cannot absorb the drugs. Whey protein is a combination of proteins that are relatively easy to digest for people living with HIV-AIDS (PHAs).

coverSupplementation with glutathione in the form of undenatured whey proteins can return glutathione levels to normal while improving the absorption of vital nutrients. By taking vitamin and mineral supplements aggressively, PHAs substantially increase their chances for a longer life.

"If there is one survival tool every HIV(+) person should consider it is taking dietary supplements that increase glutathione production." - Michael Mooney, Author, Built to Survive



Media Reports on Glutathione and Whey Protein in HIV-AIDS


When Therapies Fail: One AIDS Activist's Fight for Better Clinical Options

Neenyah Ostrom (July 11, 1999)
There are a lot of people who can survive HIV for many years with just nutraceutical support...... glutathione ratios in many patients plummet. One of those other substances that Miller has observed to produce important effects in AIDS patients is a glutathione-boosting nutraceutical. Glutathione acts as a powerful antioxidant...... If it's used with other substances that stabilize the patient's metabolism, (it) can save patients' lives, literally, because it helps stop them from developing wasting and the whole host of problems that accompany wasting syndrome.

Whey, Immunity And AIDS
Life Extension Magazine
Bounous is probably the most prolific and best known researcher in the world today regarding the use of whey protein concentrate for the prevention and treatment of cancer, AIDS and immune suppression. He has found a substantial reduction in virus activity in cells with an improved glutathione status after the ingestion of whey protein concentrate. One case in which Oxidative Stress in Cancer, AIDS, and Neurodegenerative Diseases by Luc Montagnier (Editor), Rene Olivier (Editor), Catherine Pasquier (Editor)Bournous used whey protein concentrate to treat AIDS involved an entire infected family. The wife experienced a drop in viral load from 19,000 to just 3,000 in a matter of months. Her CD4 helper T cells-the immune cells most affected by the HIV virus-rose slightly. The son in the family had a tenfold reduction in viral load, while the husband seemed to be the only semi-nonresponder in the family, with a slight drop in viral load and little change in CD4 counts. The scientific study quoted the here was also published in the book, Oxidative Stress in Cancer, AIDS, and Neurodegenerative Diseases edited by Luc Montagnier , René Olivier and Catherine Paquier

Get High on Glutathione
POZ May 2000
Oxidative stress, an ever-present problem in HIVers, can also be created by a long list of stressors, including all kinds of drugs. The more stressors you have, the more glutathione and other antioxidants you need. Yet in most HIVers, these nutrients are deficient because the body burns through them to power its immune response, repair and replace damaged and destroyed cells, and break down medications. Research shows that low levels of glutathione promote CD4-cell suicide (apoptosis). In addition, glutathione is the main detoxifier used by the liver to break down anti-HIV meds, including the Crixivan (indinavir), d4T (Zerit) and delavirdine (Rescriptor). Inadequate glutathione can compromise that liver capacity.

Whey to Go
POZ Magazine (02/97) P. 102; Burroughs, Carola

Whey, a component of milk, is a popular diet supplement among AIDS patients because it improves weight gain and provides a protein-rich energy boost while containing little lactose. Laboratory studies have shown that a new whey protein concentrate... can inhibit HIV replication while also stimulating the production of glutathione, an amino acid that helps control progression of the virus. Small trials of the treatment in HIV-positive children and adults have demonstrated its benefit.

Whey Eyed As AIDS Blocker
The Associated Press - 30 January 1996

Whey, the watery dairy product best known from the tale of Little Miss Muffet, might provide a new way to keep the AIDS virus from infecting people during sex. A modified version of a protein extracted from whey blocked the AIDS virus from infecting cells in the test tube, researchers report. For the new work, scientists modified a whey protein called beta-lactoglobulin to produce a substance they named B69. They found that B69 latched onto a protein structure called CD4 on the surface of cells. That kept the AIDS virus from using CD4 as an entryway into the cells. Someday, B69 might be put into an over-the-counter product, perhaps in combination with a virus-killing compound, he said. Neurath said preliminary work suggests B69 might block other cell sites that have been proposed as alternative entryways for HIV.

Treatment Models from India - Interview with Shashank Joshi, M.D.
John S. James, AIDS Treatment News Issue #339 March 17, 2000

"We are planning to study a nutritional supplement derived from whey protein, as a source of glutathione. It is believed that mitochondrial toxicity, which the nucleoside analog drugs and hydroxyurea may have, is mediated through the glutathione pathway. If you give patients a natural source of glutathione, maybe this problem can be prevented, and you may not see the liver toxicity, lactic acidosis, or other problems which might otherwise occur. We want to see if improved nutrition can improve the catabolic cachexia [wasting], and also we want to look for any antiretroviral effect. I understand that a small but significant number of patients has dropped their viral load by a log, after treatment with nutritional regimens designed to support the immune system."


References

  1. Decreased release of glutathione into the systemic circulation of patients with HIV infection. Helbling B, von Overbeck J, Lauterburg BH. [Eur J Clin Invest. 1996 Jan;26(1):38-44.]
  2. Molecular mechanism of decreased glutathione content in human immunodeficiency virus type 1 Tat-transgenic mice. Choi J, Liu RM, Kundu RK, Sangiorgi F, Wu W, Maxson R, Forman HJ. [J Biol Chem. 2000 Feb 4;275(5):3693-8.]
  3. Oxidative stress, HIV and AIDS. Papadopulos-Eleopulos E, Turner VF, Papadimitriou JM. [Res Immunol. 1992 Feb;143(2):145-8.]
  4. Role of cysteine and glutathione in HIV infection and other diseases associated with muscle wasting and immunological dysfunction. Droge W, Holm E. [FASEB J. 1997 Nov;11(13):1077-89.]
  5. N-acetyl-cysteine and L-2-oxothiazolidine-4-carboxylic acid enhance contact-dependent growth of HIV in resting peripheral blood mononuclear cells (PBMC) in vitro and increase recovery of HIV from human-PBMC SCID mice. Chen P, Bauer G, Mitchell J, Factor R, Markham R, Schwartz DH. [AIDS. 1997 Jan;11(1):33-41.]
  6. Can HIV infection be treated with antioxidants? Muller F. [Tidsskr Nor Laegeforen. 1995 Mar 10;115(7):835-7.]
  7. The role of oxidative stress in disease progression in individuals infected by the human immunodeficiency virus. Baruchel S, Wainberg MA. [J Leukoc Biol. 1992 Jul;52(1):111-4.]
  8. Glutathione inhibits HIV replication by acting at late stages of the virus life cycle. Palamara AT, Perno CF, Aquaro S, Bue MC, Dini L, Garaci E. [AIDS Res Hum Retroviruses. 1996 Nov 1;12(16):1537-41.]
  9. Intracellular glutathione as a possible direct blocker of HIV type 1 reverse transcription. Kameoka M, Okada Y, Tobiume M, Kimura T, Ikuta K. [AIDS Res Hum Retroviruses. 1996 Nov 20;12(17):1635-8.]
  10. Glutathione and N-acetylcysteine suppression of human immunodeficiency virus replication in human monocyte/macrophages in vitro. Ho WZ, Douglas SD. [AIDS Res Hum Retroviruses. 1992 Jul;8(7):1249-53.]
  11. Whey proteins as a food supplement in HIV-seropositive individuals. Bounous G, Baruchel S, Falutz J, Gold P. [Clin Invest Med. 1993 Jun;16(3):204-9.]
  12. Nutriceutical Modulation Of Glutathione With A Humanized Native Milk Serum Protein Isolate: Application In AIDS And Cancer. S. Baruchel, G. Viau, R. Olivier, G. Bounous, M.A. Wainberg [Oxidative Stress in Cancer, AIDS, and Neurodegenerative Diseases V Luc Montagnier et al., (Ed.) Marcel Dekker Inc., New York: 447-461, 1998 . ABSTRACT V]
  13. Improvement of immune functions in HIV infection by sulfur supplementation: two randomized trials. Breitkreutz R, Pittack N, Nebe CT, Schuster D, Brust J, Beichert M, Hack V, Daniel V, Edler L, Droge W. [J Mol Med. 2000;78(1):55-62.]
  14. Glutathione-induced enhancement of neutrophil locomotion. Elferink JG, de Koster BM. [Immunobiology. 1991 Dec;184(1):25-36.]
  15. Glutathione deficiency is associated with impaired survival in HIV disease Leonore A. Herzenberg, Stephen C. De Rosa, et al.[Proc Natl Acad Sci U S A. 1997 March 4; 94 (5): 1967-1972]
  16. Effects of long-term supplementation with whey proteins on plasma glutathione levels of HIV-infected patients. Micke P, Beeh KM, Buhl R. [Eur J Nutr. 2002 Feb;41(1):12-8.]
  17. Massive loss of sulfur in HIV infection Breitkreutz R, Holm S, Pittack N, Beichert M, Babylon A, Yodoi J, Droge W. [AIDS Res Hum Retroviruses. 2000 Feb 10;16(3):203-9.]
  18. Bioactive, Cysteine-Rich Dietary Supplement Alleviates Gastrointestinal Side-Effects with Associated Weight Gain and Marked Improvement in HAART Adherence in AIDS Patients [PDF] Pacheco L, Tidewater AIDS Crisis Task Force, Norfolk, VA, Guilford T. Journal of Human Virology, January/February, 2002, Volume 5, Number 1.
  19. CTN043: Whey Protein Supplementation in HIV-Infected Children: A Pilot Study
  20. Whey proteins as a food supplement in HIV-seropositive individuals. Bounous G, Baruchel S, Falutz J, Gold P. [Clin Invest Med. 1993 Jun;16(3):204-9.]
  21. Magnitude of body-cell-mass depletion and the timing of death from wasting in AIDS. Kotler DP, Tierney AR, Wang J, Pierson RN Jr. [Am J Clin Nutr. 1989 Sep;50(3):444-7.]
  22. Nutritional effects and support in the patient with acquired immunodeficiency syndrome. Kotler DP. [J Nutr. 1992 Mar;122(3 Suppl):723-7.]
  23. Intracellular glutathione as a possible direct blocker of HIV type 1 reverse transcription. Kameoka M, Okada Y, Tobiume M, Kimura T, Ikuta K. [AIDS Res Hum Retroviruses. 1996 Nov 20;12(17):1635-8.]
  24. Impairment of intestinal glutathione synthesis in patients with inflammatory bowel disease. Sido B, Hack V, Hochlehnert A, Lipps H, Herfarth C, Droge W. [Gut. 1998 Apr;42(4):485-92.]
  25. Cysteine and glutathione deficiency in HIV-infected patients. The basis for treatment with N-acetyl-cysteine
    Droge W. [Pharmacology. 1993;46(2):61-5.]
  26. HIV-induced cysteine deficiency and T-cell dysfunction--a rationale for treatment with N-acetylcysteine
    Droge W, Eck HP, Mihm S. [Immunol Today. 1992 Jun;13(6):211-4.]

More References:

Supplement Sheet on Whey Protein use in people with HIV/AIDS
Community AIDS Treatment Information Exchange (CATIE)

HIV (Immune Deficiency) Treatment - Disease therapies protocol
Life Extension Foundation

Glutathione Helps AIDS Survival
Proceedings of the National Academy of Sciences (1997;94:1967-1972)

Rexamining AIDS: Potential Non-Toxic Protocols
William D. Brink

Antioxidants nutrients are important in slowing the progression to AIDS from HIV infection
An interview with Dr. Luc Montagnier, the discoverer of HIV

Whey To Go! German Study Finds Whey Protein Supplement Boosts Antioxidants
Community AIDS Treatment Information Exchange (CATIE)

FDA slide show on whey isolate


Photograph of HIV - Courtesy CDC/Dr. Edwin P. Ewing, Jr.

 

 


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